SYNTHETIC PEPTIDES HAVING PITUITARY GROWTH HORMONE RELEASING ACTIVITY

Abstract: Novel peptides having the amino acid sequence selected from a group consisting of wherein X₁, X₂; and X₃ are selected from a group consisting of N-terminal and desamino alpha-carbon substitutions and a and b are 0 or 1, provided that a and b are always 0 when A₁ is a desamino residue; A₁ and A₄ are selected from a group consisting of histidyl, arginyl, lysyl α-naphthylalanyl, β-­ naphthylalanyl, isoquinolyl, tyrosyl, tryptophyl, phenyla­ anyl, homologues and analogues thereof, and, with respect to A₁ only the desamino forms thereof; A₂ and A₅ are selected from a group consisting of D-histidyl, D-arginyl, D-lysyl, D-α-naphthylalanyl, D-β-naphthylalanyl, D-­ isoquinolyl, D-tyrosyl, D-tryptophyl, D-phenylalanyl, homo­ logues and analogues thereof, and, with respect to A₅ only, the descarboxy forms thereof; A₃ is selected from a group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparginyl, glutaminyl, histidyl, D-alanyl, D-valyl, D-leucyl, D-isoleucyl, D-prolyl, D-seryl, D-threonyl, D-methionyl, D-aspartyl, D-­ glutamyl, D-asparaginyl, D-glutaminyl, D-histidyl, and homo­ logues and analogues thereof; A₆ is selected from a group consisting of amino acid residues of the L- and D- configura­ tion, homologues and analogues thereof, and the descar­ boxy forms thereof; and Y is selected from a group consisting of C-terminal and descarboxy alpha-carbon sub­ stitutions; and the pharmaceutically acceptable salts thereof; provided that (a) when (1) a is 1 and b is 0 and X₁ and X₂ are selected from the group consisting of tyrosyl, tryptophyl and phenylalanyl; (3) A₃ is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparaginyl, glutaminyl, and histidyl; and (4) Y is selected from the group consisting of -NR₁R₂, -OR, and -CH₂OR, wherein R, R₁ and R₂ are selcted from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms, then at least one of A₂ and A₅ is selected such that it is not from a group consisting of D-tyrosyl, D-tryptophyl, D-­ phenylalanyl, and, with respect to A₅, the descarboxy forms thereof; (b) when (1) a is 1 and b is 0 and X₁ and X₂ are selected from the group consisting of -H and -CH₃; (2) A₂ and A₅ are selected from the group consisting of D-tyrosyl, D-tryptophyl, D-phenylalanyl, and, with respect to A₅, the descarboxy forms thereof; (3) A₃ is seleceted from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparaginyl, glutaminyl and histidyl; and (4) Y is selected from a group consisting of -NR₁R₂, -OR, and -CH₂OR, wherein R, R₁, and R₂ are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least on of A₁ and A₄ is selected such that is not from a group consisting of tyrosyl, tryptophyl, and phenylalanyl; (c) when (1) a is 1 and b is 0 and X′₁ and X′₂ are selected from the group consisting of -H, -CH₃, and -CHOCH₃; (2) A₁ and A₄ are selected from the group consisting of tyrosyl, tryptophyl, and phenylalanyl; (3) A₃ is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, seryl, threonyl, methionyl, asparaginyl, and glutaminyl; (4) A₆ is selected from the group consisting of asparaginyl, glutaminyl, glutamyl, arginyl, lysyl, seryl, threonyl, and the descarboxy forms thereof; and (5) Y is selected from the group consisting of -NR₁R₂, -OR, and -CH₂OR, wherein R, R₁, and R₂ are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of A₂ and A₅ is selected such that it is not from a group consisting of D-tyrosyl, D-tryptophyl, and D-phenylalanyl; and (d) when (1) a is 1 and b is 0 and X′₁ and X′₂ are selected from the group consisting of -H, PCH₃, and -CHOCH₃; (2) A₂ and A₅ are selected from the group consisting of D-tyrosyl, D-­ tryptophyl, and D-phenylalanyl; (3) A₃ is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, seryl, threonyl, methionyl, asparaginyl, and glutaminyl; (4) A₆ is selected from the group consisting of asparaginyl, glutaminyl, glutamyl, arginyl, lysyl, seryl, threonyl, and the descarboxy forms thereof; and (5) Y is selected from the group consisting of -NR₁R₂, -OR, and -CH₂OR, wherein R, R₁, and R₂ are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of A₁ and A₄ is selected such that is not from a group consisting of tyrosyl, tryptophyl, and phenyl. In addition, this invention encompsasses a combination of compounds comprising (a) at least one peptide having the formula III wherein X″₁, X″₂, and X″₃ are selected from a group consisting of N-terminal and desamino alpha-carbon substi­ tutions; a and b are 0 or 1, provided that a and b are always 0 when A₁ is a desamino residue; A₁ and A₄ are selected from a group consisting of histidyl, arginyl, lysyl, α-­ naphthylanalyl, β-naphthylalanyl, isoquinolyl, tyrosyl, tryp­ tophyl, phenylalanyl, homologues and analogues thereof, and, with respect to A₁ only, the desamino forms thereof; A₂ and A₅ are selected from a group consisting of D-histidyl, D-arginyl, D-lysyl, D-α-napthylalanyl, D-tryptophyl, D-β-naphthylalanyl, D-isoquinolyl, D-tyrosyl, D-tryptophyl, D-phenylalanyl homologues and analogues thereof, and with respect to A₅ only, the descrboxy forms thereof; A₃ is selected from a group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, aspar­ aginyl, glutaminyl, histidyl, D-alanyl, D-valyl, D-leucyl, D-­ isoleucyl, D-prolyl, D-seryl, D-threonyl, D-methionyl, D-­ aspartyl, D-glutamyl, D-asparaginyl, D-glutaminyl, D-hystidyl, and homologues and analogues thereof; A₆ is selected from a group consisting of amino acid residues of the L- and D-configuration, homologues and analogues thereof, and the descarboxy forms thereof; and Y is selected from a group consisting of C-terminal and descarboxy alpha-carbon sub­ stitutions; and the pharmaceutically acceptable salts thereof; and (b) at least one growth promoting agent. Combinations comprising at least one of the above-­ described peptides and at least one growth promoting agent. These peptides and combinations act directly on the pituitary to release growth hormone therefrom.

Description: SYNTHETIC PEPTIDES HAVING PITUITARY GROWTH HORMONE RELEASING ACTIVITY Background of the Invention 1. Field of the Invention This invention'relates to peptides which possess pituitary growth hormone releasing activity and to combinations comprising at least one peptide and at least one growth promoting agent, which combination possesses synergistic pituitary growth hormone releasing activity. 2. Description of the Prior Art Growth hormone, which is secreted from the pituitary, causes growth of all tissues of the body that are capable of growing. In addition, growth hormone is known to have the following basic effects on the metabolic process of the body: 1. Increased rate of protein synthesis in all cells of the body; 2. Decreased rate of carbohydrate utilization in cells of the body; 3. Increased mobilization of free fatty acids and use of fatty acids for energy. A deficiency in growth hormone secretion can result in various medical disorders, such as some instances of dwarfism. Various ways are known to release growth hormone. For example, chemicals such as arginine, L-3,4dihydroxyphenylalanine (L-DOPA), glucagon, vasopressin, and insulin induced hypoglycemia, as well as activities such as sleep and exercise, indirectly cause growth hormone to be released from the pituitary by acting in some fashion on the hypothalamus perhaps either to decrase somatostatin secretion or to increase an unknown endogenous growth hormone-releasing hormone or both. Compounds which directly act on the pituitary to release growth hormone include prostaglandin E1 and E2, theophylline, and cyclic nucleotides. However, these compounds neither specifically release growth hormone nor are they believed to act at the putative growth hormonereleasing hormone receptors in the peripheral membrane of the pituitary cell to initiate growth hormone release. In addition, under special conditions certain chemically defined peptides, e.g., vasopressin, thyrotropin-releasing hormone (TRH), luteinizing hormone-releasing hormone (LH-RH), a-melanocyte-stimulating hormone (a MSH), glucagon, substance P, neurotensin; Met-enkephalin, a-endorphin, chlorea-enterotoxin, and basic myelin protein, act to release growth hormone from the pituitary. However, only TRH acts directly on the pituitary to elicit this response. Furthermore, the above listed peptides release other pituitary hormones and under most experimental conditions do not release growth hormone. For example, TRH does not release growth hormone in normal rats or in normal humans or from pituitaries of normal rats or monkeys. In vitro, TRH releases growth hormone, prolactin, and thyroid stimulating hormone (TSH) in certain species, and, in vivo, TRH releases these hormones from bovine pituitary. Vasopressin's induced release of growth hormone is considered to be due to a non-specific response to stress caused by administration of high dosages of vasopress in. Accordingly it would be highly desirable to have a compound or combination of compounds which directly acts on the pituitary under normal experimental conditions to effect the release of growth hormone therefrom. Such compound or combination of compounds would be useful in vitro, e.g., as unique research tools for understanding how growth hormone secretin is regulated at the pituitary level and would also be useful in vivo, e.g., to treat symptoms related to growth hormone deficiencies, to increase the rate and extent of growth in commercial animals, to increase milk yield in commercial animals, and to reduce the number of mucosal erosions induced by hypoxemia. Summary of the Invention In accordance with the present invention there is provided peptides which act directly on the pituitary under normal experimental conditions in vitro to release growth hormone therefrom. In addition, there is provided a combination of compounds which act directly on the pituitary under normal experimental conditions in vitro to synergistically release growth hormone therefrom. These growth hormone releasing compounds and combinations can be utilized in vitro as unique research tools for understanding, inter alia, how growth hormone secretion is regulated at the pituitary level. Also, the growth hormone releasing peptides of the instant invention can also be administered in vivo to increase growth hormone release. More particularly, this invention encompasses novel peptides having the formulas I and II EMI3.1 EMI4.1 wherein X1, X2, X3, and X1', X21, and X3' are selected from a group consisting of N-terminal and desamino alphacarbon substitutions; a and b are 0 or 1, provided that a and b are always 0 when A1 is a desamino residue; A1 and A4 are selected from a group consisting of histidyl, arginyl, lysyl, a-naphthylalanyl, B-naphthylalanyl, isoquinolyl, tyrosyl, tryptophyl, phenylalanyl, homologues and analogues thereof, and, with respect to Al only, the desamino forms thereof; A2 and As are selected from a group consisting of D-histidyl, D-arginyl, D-lysyl, D-anaphthylalanyl, D-8-naphthylalanyl, D-isoquinolyl, Dtyrosyl, D-tryptophyl, D-phenylalanyl, homologues and analogues thereof, and, with respect to Assonly, the descarboxy forms thereof; A3 is selected from a group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparaginyl,glutaminyl, histidyl, D-alanyl, D-valyl, Dleucyl, D-isoleucyl, D-prolyl, D-seryl, D-threonyl, Dmethionyl, D-aspartyl, D-glutamyl, D-asparaginyl, Dgl-utaminyl, D-histidyl, and homologues and analogues thereof; A6 is selected from a group consisting of amino acid redisues of the L- and D-configuration, homologues and analogues thereof, and the descarboxy forms thereof; and Y is selected from a group consisting of C-terminal and descarboxy alpha-carbon subtitutions; and the pharmaceutically acceptable salts thereof; provided that (a) when (1) is 1 and b is 0 and X1 and X2 are selected from the group consisting of tyrosyl, tryptophyl, and phenylalanyl; (3) A3 is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparaginyl, glutaminyl, and histidyl; and (4) Y is selected from the group consisting of -NR1R2, -OR, and -CH20R, wherein R, R1, and R2 are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of A2 and As is selected such that it is not from a group consisting of D-tyrosyl, D-tryptophyl, Dphenylalanyl, and, with respect to As, the descarboy forms thereof; (b) when (1) a is 1 and b is 0 and X1 and are selected from the group consisting of -H and -CH3; (2) A2 and As are selected from the group consisting of D-tyrosyl., D-tryptophyl, D-phenylalanyl, and, with respect to As, the descarboxy forms thereof; (3) A3 is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparaginyl, glutaminyl and histidyl; and (4) Y is selected from the group consisting of -NR1R2, -OR, and -CH20Rj wherein R, R1, and R2 are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of A1 and A4 is selected such that it is not from a group consisting of tyrosyl, tryptophyl, and phenylalanyl; (c) when (1) a is 1 and b is 0 and X11 and X2 are selected from the group consisting of -H, -CH3, and -CHOCH3; (2) A1 and A4 are selected from the group consisting of tyrosyl, tryptophyl, and phenylalanyl; (3) A3 is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, seryl, threonyl, methionyl, asparaginyl, and glutaminyl; (4) A6 is selected from the group consisting of asparaginyl, glutaminyl, glutamyl, arginyl, lysyl, seryl, threonyl, and the descarboxy forms thereof; and (5) Y is selected from the group consisting of -NR1R2, -OR, and -CH2OR, wherein R, R1, and R2 are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of A2 and As is selected such that it is not from a group consisting of D-tyrosyl, D-tryptophyl, and D-phenylalanyl; and (d) when (1) a is 1 and b is 0 and X1' and X21 are selected from the group consisting of -H, -CH31 and -CHOCH3; (2) A2 and As are selected from the group consisting of D-tyrosyl, D-tryptophyl, and Dphenylalanyl; (3) A3 is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, seryl, threonyl, methionyl, asparaginyl, and glutaminyl; (4) A6 is selected from the group consisting of asparaginyl, glutaminyl, glutamyl, arginyl, lysyl, seryl, threonyl, and the descarboxy forms thereof; and (5) Y is selected from the group consisting of -NR1R2, -OR, and -CH2OR, wherein R, R1, and R2 are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of A1 and A4 is selected such that it is not from a group consisting of tyrosyl, tryptophyl, and phenylalanyl. In addition, this invention encompasses a combination of compounds comprising (a) at least one peptide having the formula III EMI6.1 wherein X1" r X2", and X3" are selected from a group consisting of N-terminal and desamino alpha-carbon substitutions; a and b are 0 or 1, provided that a and b are always 0 when A1 is a desamino residue; A1 and A4 are selected from a group consisting of histidyl, arginyl, lysyl, a-naphthylalanyl, a-naphthylalanyl, isoquinolyl, tryosyl, tryptophyl, phenylalanyl, homologues and analogues thereof, and, with respect to A1 only, the des amino forms thereof; A2 and As are selected from a group consisting of D-histidyl, D-arginyl, D-lysyl, D-anaphthylalanyl, D-B-naphthylalanyl, D-isoquinolyl, Dtyrosyl, D-tryptophyl, D-phenylalanyl, homologues and analogues thereof, and, with respect to A5 only, the descarboxy forms thereof; A3 is selected from a group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparaginyl, glutaminyl, histidyl, D-alanyl, D-valyl, Dleucyl, D-isoleucyl, D-prolyl, D-seryl, D-threonyl, Dmthionyl, D-aspartyl, D-glutamyl, D-asparaginyl, D-glutaminyl, D-histidyl, and homologues and analogues thereof; A6 is selected from a group consisting of amino acid residues of the L- and D-configuration, homologues and analogues thereof, and the descarboxy forms thereof; and Y is selected from a group consisting of C-terminal and descarboxy alpha-carbon substitutions; and the pharmaceutically acceptable salts thereof; and (b) at least one growth promoting agent. Detailed Description of the Preferred Embodiments The peptides of this invention have the amino acid residue sequence represented by formulas I-III, supra. All amino acid residues identified herein are in the natural or L-configuration unless otherwise specified. Abbreviations for amino acid residues are used in accordance with the following standard peptide nomenclature: Tyr L-tyrosyl Ile L-isoleucyl D-Tyr D-tyrosyl D-Ile D-isoleucyl Gly glycyl Leu L-leucyl Phe L-phenylalanyl D-Leu D-leucyl D-Phe D-phenylalanyl Thr L-threonyl Met L-methionyl D-Thr D-threonyl D-Met D-methionyl Val L-valyl Ala L-alanyl D-Val D-valyl D-Ala D-alanyl Pro L-prolyl Ser L-seryl D-Pro D-prolyl D-Ser D-seryl Gln L-glutaminyl Lys L-lysyl D-Gln D-glutaminyl D-Lys D-lysyl Glu L-glutamyl Asn L-asparaginyl D-Glu D-glutamyl D-Asn D-asparaginyl Trp L-tryptophyl His L-histidyl D-Trp D-tryptophyl L-Asp L-aspartyl D-His D-histidyl D-Asp D-aspartyl Cys L-cysteinyl Arg L-arginyl D-Cys D-cysteinyl D-Arg D-arginyl Hypro L-hydroxypropyl D-Hypro D-hydroxypropyl Dopa L-3,4-dihydroxy phenylalanyl L- < Glu L-pyroglutamyl D-Dopa D-3,4-dihydroxy phenylalanyl D- < Glu D-pyroglutamyl Hylys L-6-hydroxylysyl Sar N-methylglycyl (sarcosyl) D-Hylys D-a-methylalanyl Aib L-a-methylalanyl a-Naphth L--naphthyl- (L-aminoisobutyryl) alanyl D-a-Naphth D-a-naphthyl alanyl B-Naphth L-ss-naphthyl- alanyl Iql L-isoquinolyl D-B-Naphth D-ss-naphthyl- D-Iql D-isoquinolyl alanyl Virtually any suitable N-terminal and desamino alpha-carbon substitution can be used in the instant invention as represented by the various structural formulas set forth herein. Typical N-terminal and desamino alpha-carbon substitutions include, but are not limited to, those set forth in Table I. TABLE I N-Terminus and Desamino Alpha-Carbon Substitutions1 N-Terminus Substitutions EMI9.1 <tb> <SEP> X1 <SEP> X2 <SEP> X3 <SEP> a <SEP> b <tb> <SEP> R1- <SEP> R2- <SEP> - <SEP> 1 <SEP> 0 <tb> <SEP> R1- <SEP> R2- <SEP> R3 <SEP> 1 <SEP> 1 <tb> <SEP> 0 <tb> <SEP> II <tb> R1-Z-C- <SEP> R2- <SEP> - <SEP> 1 <SEP> 0 <tb> <SEP> 0 <tb> <SEP> II <tb> R1-C- <SEP> R2- <SEP> - <SEP> 1 <SEP> 0 <tb> R1- <SEP> HO- <SEP> - <SEP> 1 <SEP> 0 <tb> <SEP> R2 <tb> <SEP> l <tb> R1-N- <SEP> R3- <SEP> - <SEP> 1 <SEP> 0 <tb> <SEP> R2 <SEP> Z <tb> <SEP> IJ <tb> R1-N <SEP> - <SEP> C- <SEP> R3- <SEP> - <SEP> 1 <SEP> 0 <tb> <SEP> Desamino <SEP> Alpha-Carbon <SEP> Substitutions <tb> R- <SEP> - <SEP> - <SEP> 0 <SEP> 0 <tb> RZ- <SEP> O <SEP> 0 <SEP> 0 <tb> 1. LEGEND: R, R1 , R2, and R3 are selected from a group consisting of hydrogen; straight and branched chain alkyl groups having from 1 to 6 carbon atoms; cyclo alkyl groups having from 3 to 6 carbon atoms; benzyl; benzhydryl; trityl; aryl; alkoxybenzyl; al koxybenzhydryl; alkoxytrityl; lower haloalkyl groups having from 1 to 6 carbon atoms; halobenzyl; halo benzhydryl; halotrityl; haloaryl; and cyclohaloalkyl groups having from 3 to 6 carbon atoms. Preferably, R, R1, R2, and R3 are selected from the group con sisting of hydrogen and alkyl groups having from 1 to 6 carbon atoms. More preferably, R, R1, R2, and R3 are selected from the group consisting of hydro gen and alkyl groups having 1 to 2 carbon atoms. Z is selected from a group consisting of oxygen and sulfur. Z is preferably oxygen. Virtually any suitable C-terminal and descarboxy alpha-carbon substitution can be used in the instant invention as represented by the various structural formulas set forth herein. Typical C-terminal and descarboxy alpha-carbon substitutions include, but are not limited to, those also set forth in Table II. TABLE II C-Terminus and Descarboxy Alpha-Carbon Substitutionsl C-Terminus Substitutions -OR R1 -N-R2 -R EMI10.1 Descarboxy Alpha-Carbon Substitutions EMI11.1 1. LEGEND: R, R1, R2, and R3 are as defined in Table I, supra. V is selected from a group consisting of oxy gen, sulfur, and nitrogen. V is preferably oxygen. The structure of amino acid residues employed in the peptides of this invention are set forth in Table III. Typical homologues and analogues of these amino acid residues which can also be employed in the peptides of this invention include, but are not limited to, those listed in Table III. TABLE III L or D Amino Acid Residue EMI12.1 SUBSTITUENTS OF NAME NATURAL SUBSTITUENTS HOMOLOGUES & ANALOGUESÚ Ra Rb Rc Ra Rb Rc Gly -H -H -H -H U U1 Ala -CH3 -H -H -CH3 U U1 =CH2 - U Val -CH(CH3)2 -H -H -CH(CH3)2 U U1 -C(CH3)3 U U1 =C(CH3)2 - U Leu -CH2CH(CH3)2 -H -H -(CH2)n+1CH(CH3)2 U U1 -(CH2)n+1C(CH3)3 U U1 =CHCH(CH3)2 - U =CH(CH2)nCH(CH3)2 - U TABLE III (contd.) EMI13.1 <SEP> SUBSTITUENTS <SEP> OF <tb> NAME <SEP> NATURAL <SEP> SUBSTITUENTS <SEP> HOMOLOGUES <SEP> & ANALOGUESÚ <tb> <SEP> Ra <SEP> Rb <SEP> Rc <SEP> Ra <SEP> Rb <SEP> Rc <tb> <SEP> CH3 <SEP> CH3 <tb> <SEP> # <SEP> # <tb> Ile <SEP> -CH-C2H5 <SEP> -H <SEP> -H <SEP> -CH-C2H5 <SEP> U <SEP> U1 <tb> NIle <SEP> -CH2CH2CH2CH3 <SEP> -H <SEP> -H <SEP> -(CH2)n+1CH3 <SEP> U <SEP> U1 <tb> <SEP> =CH(CH2)nCH3 <SEP> - <SEP> U <tb> Pro <SEP> CH2----CH2--------CH2 <SEP> CH2-----(CH2)n--------CH2 <tb> <SEP> # <SEP> -H <SEP> # <SEP> # <SEP> U <SEP> # <tb> <SEP> CH2-----CH# <SEP> CH <tb> <SEP> # <SEP> U1 <SEP> # <tb> <SEP> CH2-----CHOU----------CH2 <tb> <SEP> # <SEP> U <SEP> # <tb> <SEP> (CH2)n--B-----------(CH2) <tb> <SEP> # <SEP> U <SEP> # <tb> Ser <SEP> -CH2OH <SEP> -H <SEP> -H <SEP> -(CH2)n+1OU <SEP> U1 <SEP> U2 <tb> Thr <SEP> -CHOH-CH3 <SEP> -H <SEP> -H <SEP> -(CH2)n+1CHOU-CH3 <SEP> U1 <SEP> U2 <tb> TABLE III (contd.) SUBSTITUENTS OF NAME NATURAL SUBSTITUENTS HOMOLOGUES & ANALOGUESÚ Ra Rb Rc Ra Rb Rc Cys -CH2SH -H -H -(CH2)n+1SU U1 U2 -(CH2)n+1SO3H U U1 Met -CH2CH2SCH3 -H -H -(CH2)n+1SCH3 U U1 =CH(CH2)n+1SCH3 - U1 -(CH2)n+1SOCH3 U U1 =CH(CH2)n+1SOCH3 - U1 -(CH2)n+1SO2CH3 U U1 =CH(CH2)n+1SO2CH3 - U Asp -CH2COH -H -H -(CH2)n+1CO2U U1 U2 =CH(CH2)nCO2U - U1 Glu -CH2CO2H -H -H -(CH2)n+1CO2U U1 U2 Asn -CH2CONH2 -H -H -(CH2)n+1CONR1R2 U U1 =CH(CH2)nCONR1R2 - U Gln -(CH2)2CONH2 -H -H -(CH2)n+1CONR1R2 U U1 TABLE III (contd.) EMI15.1 <SEP> SUBSTITUENTS <SEP> OF <tb> NAME <SEP> NATURAL <SEP> SUBSTITUENTS <SEP> HOMOLOGUES <SEP> & ANALOGUESÚ <tb> <SEP> Ra <SEP> Rb <SEP> Rc <SEP> Ra <SEP> Rb <SEP> Rc <tb> Arg <SEP> -(CH2)3NH-C=NH <SEP> -H <SEP> -H <SEP> -(CH2)n+1NU-C=ND <SEP> U1 <SEP> U2 <tb> <SEP> # <SEP> # <tb> <SEP> NH2 <SEP> N-D1 <tb> <SEP> # <tb> <SEP> D2 <tb> <SEP> -(CH2)n+1NUC===N-D2 <SEP> U1 <SEP> U2 <tb> <SEP> # <SEP> # <tb> <SEP> N-D <SEP> D3 <tb> <SEP> # <tb> <SEP> D1 <tb> Lys <SEP> -(CH2)4NH2 <SEP> -H <SEP> -H <SEP> -(CH2)n+1N-U2 <SEP> U <SEP> U3 <tb> <SEP> # <tb> <SEP> U1 <tb> <SEP> U1 <tb> <SEP> # <tb> <SEP> -(CH2)n+1N-U2 <SEP> U <SEP> U4 <tb> <SEP> # <tb> <SEP> U3 <tb> His <SEP> -CH2###NH <SEP> -H <SEP> -H <SEP> -(CH2)n+1###N-D <SEP> U <SEP> U1 <tb> <SEP> #N# <SEP> #N# <tb> <SEP> -(CH2)n+1####N <SEP> U <SEP> U1 <tb> <SEP> #N-D <tb> TABLE III (contd.) EMI16.1 SUBSTITUENTS <SEP> OF <tb> NAME <SEP> NATURAL <SEP> SUBSTITUENTS <SEP> HOMOLOGUES & NALOGUESÚ <tb> <SEP> Ra <SEP> Rb <SEP> Rc <SEP> Ra <SEP> Rb <SEP> Rc <tb> <SEP> -(CH2)n+1-#-N-D <SEP> U <SEP> U1 <tb> <SEP> # <tb> <SEP> +N-D <tb> <SEP> -(CH2)n+1-#- <SEP> U <SEP> U1 <tb> <SEP> #N <tb> <SEP> N-D <tb> <SEP> -(CH2)n+1-#- <SEP> U <SEP> U1 <tb> <SEP> #N-D <tb> <SEP> N <tb> <SEP> -(CH2)n+1-#- <SEP> U <SEP> U1 <tb> <SEP> D-N# <tb> <SEP> N <tb> <SEP> -(CH2)n+1-#- <SEP> U <SEP> U1 <tb> <SEP> N# <tb> <SEP> N-D <tb> <SEP> -(CH2)n+1-#- <SEP> U <SEP> U1 <tb> <SEP> # <tb> <SEP> B <tb> TABLE III (contd.) EMI17.1 <SEP> SUBSTITUENTS <SEP> OF <tb> NAME <SEP> NATURAL <SEP> SUBSTITUENTS <SEP> HOMOLOGUES <SEP> & NALOGUESÚ <tb> <SEP> Ra <SEP> Rb <SEP> Rc <SEP> Ra <SEP> Rb <SEP> Rc <tb> <SEP> -(CH2)n+1-#-----# <SEP> U <SEP> U1 <tb> <SEP> #-B-L-# <tb> <SEP> -(CH2)n+1-#-----# <SEP> U <SEP> U1 <tb> <SEP> #-L-B-# <tb> <SEP> -(CH2)n+1-#-----# <SEP> U <SEP> U1 <tb> <SEP> #-B-L-# <tb> <SEP> -(CH2)n+1-#-----L <SEP> U <SEP> U1 <tb> <SEP> #-----B <tb> <SEP> # <tb> <SEP> N <SEP> N-D <tb> <SEP> #----# <tb> <SEP> CH2 <SEP> U <SEP> CH2 <tb> <SEP> # <tb> <SEP> D-N <SEP> N <tb> <SEP> #---# <tb> <SEP> CH2 <SEP> U <SEP> CH2 <tb> TABLE III (contd.) EMI18.1 <SEP> SUBSTITUENTS <SEP> OF <tb> NAME <SEP> NATURAL <SEP> SUBSTITUENTS <SEP> HOMOLOGUES <SEP> & NALOGUESÚ <tb> <SEP> Ra <SEP> Rb <SEP> Rc <SEP> Ra <SEP> Rb <SEP> Rc <tb> <SEP> #K1--K2# <SEP> U <SEP> U1 <tb> Phe <SEP> -CH2 <SEP> -H <SEP> -H <SEP> -(CH2)n+1#------#K3 <tb> <SEP> # <SEP> #K5#K4-# <tb> <SEP> #K1--K2# <tb> <SEP> =CH(CH2)n-#-----#K3 <SEP> - <SEP> U1 <tb> <SEP> #K5-#-K4 <tb> <SEP> #K2--K3# <tb> <SEP> #------# <tb> <SEP> K1-------K4 <tb> <SEP> #------# <tb> <SEP> CH2 <SEP> CH2 <SEP> U1 <tb> <SEP> # <SEP> # <tb> Tyr <SEP> -CH2 <SEP> -H <SEP> -H <SEP> See <SEP> Phe <SEP> above <tb> <SEP> # <tb> <SEP> OH <tb> TABLE III (contd.) EMI19.1 <SEP> SUBSTITUENTS <SEP> OF <tb> NAME <SEP> NATURAL <SEP> SUBSTITUENTS <SEP> HOMOLOGUES <SEP> & NALOGUESÚ <tb> <SEP> Ra <SEP> Rb <SEP> Rc <SEP> Ra <SEP> Rb <SEP> Rc <tb> &alpha; ;-Naphth <SEP> -CH2 <SEP> -H <SEP> -H <SEP> -(CH2)n+1 <SEP> U <SEP> U1 <tb> <SEP> ## <SEP> ## <SEP> ## <tb> <SEP> K1 <SEP> K6 <tb> <SEP> # <SEP> # <tb> <SEP> K2 <SEP> K5 <tb> <SEP> # <SEP> # <SEP> # <tb> <SEP> K3 <SEP> K4 <tb> <SEP> #CH <SEP> - <SEP> U <tb> <SEP> # <SEP> K7# <tb> <SEP> K1 <SEP> K6 <tb> <SEP> # <SEP> # <tb> <SEP> K2 <SEP> K5 <tb> <SEP> # <SEP> # <SEP> # <tb> <SEP> K3 <SEP> K4 <tb> TABLE III (contd.) EMI20.1 <SEP> SUBSTITUENTS <SEP> OF <tb> NAME <SEP> NATURAL <SEP> SUBSTITUENTS <SEP> HOMOLOGUES <SEP> & NALOGUESÚ <tb> <SEP> Ra <SEP> Rb <SEP> Rc <SEP> Ra <SEP> Rb <SEP> Rc <tb> ss-Naphth <SEP> -CH2-## <SEP> -H <SEP> -H <SEP> K7 <SEP> K6 <tb> <SEP> # <SEP> # <tb> <SEP> # <SEP> K5 <SEP> U <SEP> U1 <tb> <SEP> -(CH2)-# <SEP> # <tb> <SEP> K1 <SEP> K4 <tb> <SEP> # <SEP> # <SEP> # <tb> <SEP> K2 <SEP> K3 <tb> <SEP> K7 <SEP> K6 <tb> <SEP> # <SEP> # <tb> <SEP> # <SEP> K5 <SEP> - <SEP> U <tb> <SEP> #CH-----# <SEP> # <tb> <SEP> K1 <SEP> K4 <tb> <SEP> # <SEP> # <SEP> # <tb> <SEP> K2 <SEP> K3 <tb> <SEP> K1 <tb> Trp <SEP> -CH2-## <SEP> -H <SEP> -H <SEP> -(CH2)n+1-# <SEP> # <tb> <SEP> # <SEP> K2 <SEP> U <SEP> U1 <tb> <SEP> # <SEP> # <tb> <SEP> # <SEP> # <SEP> K3 <tb> <SEP> # <SEP> # <tb> <SEP> L <SEP> K4 <tb> Sor <SEP> -H <SEP> -H <SEP> -CH3 <SEP> U <SEP> U1 <SEP> -CH3 <tb> <SEP> K1 <tb> Igl <SEP> -CH2-## <SEP> -H <SEP> -H <SEP> -(CH2)n+1-# <SEP> # <SEP> U <SEP> U1 <tb> <SEP> # <SEP> K2 <tb> <SEP> # <SEP> # <SEP> # <tb> <SEP> # <SEP> K3 <tb> <SEP> # <SEP> # <tb> <SEP> L <SEP> K4 <tb> 1. LEGEND: U, U1, U2, U3 and U4 are selected from a group consisting of hydrogen, alkyl groups having from 1-10 carbon atoms, and benzyl. B, B1, and B2 are selected from a group consisting of -N-D, O, S. D, D1, D21 and D3 are selected from a group consisting of hydrogen, methyl, ethyl, propyl, benzyl, formyl, and tosyl. K1, K2, K3, K4, Ks, K6, and K7 are N or -C-G, provided that adjacent positions are not both N. G is selected from a group consisting of hydrogen, halogen, -OU, -ORx, -SRx, -Rx,-SO3Rx, -B(OH)1, -RNxSORy, -NRxRy, -C#N, -N(Rx)CORy, wherein RX and Ry are selected from a group consisting of hydrogen and straight and branched alkyl groups containing 1-6 carbon atoms, and substituted straight and branched alkyl groups containing 1-6 carbon atoms, wherein the substituents include, but are not limited to, one or more halo, hydroxy, amino, and mercapto groups. L is -N or -N+-D. R1 and R2 are as defined in Table I. n is an integer from 0 to 4. The term ffpharmaceutically acceptable salts", as used herein, refers to the non-toxic alkali metal, alkaline earth metal and ammonium salts commonly used in the pharmaceutical industry including, but not limited to, the sodium, potassium, lithium, calcium, magnesium, barium, ammonium and protamine salts which are prepared by methods well known in the art. The term also includes non-toxic acid addition salts which are generally prepared by reacting the compounds of this invention with a suitable organic or inorganic acid. Representative salt include, but are not limited to, the hydrochloride, hydrobromide, sulfate, bisulfate, acetate, oxalate, valerate, oleate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, napsylate, and the like. Preferably, the peptides of formula I of this invention have the amino acid sequence wherein a is O or 1, b is 0 and X1 and X2 are selected from a group consisting of -R, -OR, and RC(O)-, wherein R is selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; A1 and A4 are selected from the group consisting of histidyl, tryptophyl, phenylalanyl, tyrosyl, homologues and analogues thereof, and, with respect to A1, the desamino forms thereof; A2 and Ag are selected from the group consisting of D-histidyl, D-tryptophyl, D-phenylalanyl, D-tyrosyl, homologues and analogue thereof, and, with respect to A5, the descarboxy forms thereof; A3 is selected from the group consisting of glycyl, alanyl, seryl, asparaginyl, prolyl, D-alanyl, D-seryl, Dasparaginyl, D-prolyl, and homologues and analogues thereof; Y is selected from a group consisting of -CH2OH, -OR, and -NR1R2, wherein R, R1, and R2 are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; and the pharmaceutically acceptable salts thereof. Preferably, the peptides of formulas II and III of this invention have the amino acid sequence wherein a is O or 1, b is 0 and X1', X21, Xii', and X2" are selected from a group consisting of -R, -OR, and RC(O)-, wherein R is selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; A1 and A4 are selected from the group consisting of histidyl, tryptophyl, phenylalanyl, tyrosyl, homologues and analogues thereof, and, with respect to A1, the desamino forms thereof; A2 and As are selected from the group consisting of D-histidyl, D-tryptophyl, Dphenylalanyl, D-tyrosyl, homologues and analogues thereof; A3 is selected from the group consisting of glycyl, alanyl, seryl, asparaginyl, prolyl, D-alanyl, D-seryl, Dasparaginyl, D-prolyl, and homologuess and analogues thereof; A6 is selected from the group consistng of arginine, lysine, ornithine, histidine, aspartic acid, glutamic acid, asparagine, glutamine, D-arginine, Dlysine, D-orthithine, D-histidine, D-aspartic acid, Dglutamic acid, D-asparagine, D-glutamine, D-arginine, homologues and analogues thereof, and the descarboxy forms thereof; Y is selected from a group consisting of -CH20H, -OR, and -NR1R2, wherein R, Ri, and R2 are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; and the pharmaceutically acceptable salts thereof. More preferably, the peptides of (a) formula I and (b) formulas II and III of this invention have the amino acid sequence represented by formulas IV and V, respectively: EMI24.1 wherein a is O or 1; X2 is selected from the group consisting of R- and RC(O)-; wherein R is selected from the group consisting of hydrogen and alkyl groups containing 1-2 carbon atoms; A1 is selected from the group consisting of tyrosyl, O-methyltyrosyl, histidyl, 3-N-methylhistidyl, p-chlorophenylalanyl, and the desamino forms thereof; A3 is selected from the group consisting of alanyl, seryl, and D-alanyl; A4 is selected from the group consisting of tryptophyl and tyrosyl; As is selected from the group consisting of D-phenylalanyl, Dhistidyl, D-tyrosyl, and D-p-chlorophenylalanyl; A6 is selected from the group consisting of arginine, homoarginine, lysine, ornithine, aspartic acid, glutamic acid, asparagine, glutamine, and D-lysine; and Y is selected from the group consisting of -OR and -NHR, wherein R is selected from the group consisting of hydrogen and alkyl groups containing 1-2 carbon atoms; and the pharmaceutically acceptable salts thereof. Peptides within the scope of the instant invention include, but are not limited to, those set forth in Table IV and the desamino and/or descarboxy forms'thereof, wherein the respective positions of (a) X1, X2, X3, (b) X1', X2', X31, and (c) X1", X2", X3" are set forth in formulas I-III, respectively. TABLE IV (X1-, (X2-)a, (X3-)b)-His-D-Trp-Ala-Trp-D-Phe-Y (X1-, (X2-)a, (X3-)b)-His-D-5-Br-Trp-Ala-Trp-D-Phe-Y (X1-,(X2-)a,(x3-)b)-His-D-Trp-Ala-5-Br-Trp-D-phe-y (X1-, (X2-)a, (X3-)b)-1-N-Me-His-D-Trp-Ala-Trp-D-Phe-Y (X1-, (X2-)a, (X3-)b)-3-N-Me-His-D-Trp-Ala-Trp-D-Phe-Y (X1-, (X2-)a, (X3-)b)-Arg-D-Trp-Ala-Iql-D-Phe-Y (X1-, (X2-)a, (X3-)b)-Lys-D-Trp-Ala-Trp-D-Phe-Y (X1-, (X2-)a, (X3-)b)-His-D-Trp-Ser-Trp-D-Phe-Y (X1-, (X2-)a, (X3-)b)-Tyr-D-Trp-S-Ala-Trp-D-His-Y (X1-, (X2-)a, (X3-)b)-Tyr-D-Trp-Ala-Trp-D-1-N-Me-His-Y (X1-, (X2-)a, (X3-)b)-Tyr-D-Trp-Ala-Trp-D-3-N-Me-His-Y (X1-, (X2-)a, (X3-)b)-Tyr-D-Trp-Ala-Trp-D-Arg-Y (X1-, (X2-)a, (X3-)b)-Tyr-D-Trp-Ala-Trp-D-Lys-Y (X1-, (X2-)a, (X3-)b)-Tyr-D-Trp-D-Ser-Trp-D-Lys-Y (X1-, (X2-)a, (X3-)b)-His-D-Trp-Ala-Trp-D-His-Y (X1-, (X2-)a, (X3-)b)-Arg-D-Phe-Val-Tyr-D-Lys-Y (X1-, (X2-)a, (X3-)b)-Tyr-D-Tyr-Met-Phe-D-Arg-Y (X1-, (X2-)a, (X3-)b)-Phe-D-Phe-Gln-Phe-D-1-N-Me-His-Y (X1-, (X2-)a, (X3-)b)-His-D-Trp-Ile-Tyr-D-Trp-Y (X1-, (X2-)a, (X3-)b)-&alpha;-Naphth-D-Trp-S-Ala-ss-Naphth-D-Phe-Y (X1-, (X2-)a, (X3-)b)-ss-Naphth-D-Lys-His-D-Arg-Y (X1'-, (X2'-)a, (X3'-)b)-His-D-Trp-Ala-Trp-D-Phe-Lys-Y (X1'-, (X2'-)a, (X3'-)b)-His-D-5-Br-Trp-Ala-Trp-D-Phe-Lys-Y (X1'-, (X2'-)a, (X3'-)b)-His-D-Trp-Ala-5-Br-Trp-D-Phe-Lys-Y (X1'-, (X2'-)a, (X3'-)b)-1-N-Me-His-D-Ala-Trp-D-Phe Asn-Y (X1'-, (X2'-)a, (X3'-)b)-3-N-Me-His-D-Trp-Ala-Trp-D-Phe Lys-Y (X1'-, (X2'-)a, (X3'-)b)-Arg-D-Trp-Ala-Iql-D-Phe-Arg-Y (X1'-, (X2'-)a, (X3'-)b)-Lys-D-Trp-Ala-Trp-D-Phe-Glu-Y (X1'-, (X2'-)a, (X3'-)b)-His-D-Trp-Ser-Trp-D-Phe-Lys-Y (X1'-, (X2'-)a, (X3'-)b)-Tyr-D-Trp-D-Ala-Trp-D-His-Gln-Y (X1'-, (X2'-)a, (X3'-)b)-Tyr-D-Trp-Ala-Trp-D-1-N-Me-His Met-Y (X1'-, (X2'-)a, (X3'-)b)-Tyr-D-Trp-Ala-Trp-D-3-N-Me-His Pro-Y (X1'-, (X2'-)a, (X3'-)b)-Tyr-D-Ala-Trp-D-Arg-His-Y (X1'-, (X2'-)a, (X3'-)b)-Tyr-D-Ala-Trp-D-Lys-Ser-Y (X1'-, (X2'-)a, (X3'-)b)-Tyr-D-Trp-D-Ser-Trp-Phe-Y (X1'-, (X2'-)a, (X3'-)b)-His-D-Trp-Ala-Trp-D-His-Trp-Y (X1'-, (X2'-)a, (X3'-)b)-Arg-D-Phe-Val-Tyr-D-Lys-Y-Lys-D (X1'-, (X2'-)a, (X3'-)b)-Tyr-D-Tyr-met-Phe-D-Arg-D-Orn-Y (X1'-, (X2'-)a, (X3'-)b)-Phe-D-Phe-Gln-Phe-D-1-N-Me-His-D Asp-Y (X1 -,(X2 ¯)a,(X3 -)b)-His-D-Trp-Ile-Tyr-D-Trp-D-Glu-y (X1'-, (X2'-)a, (X3'-)b)-&alpha;-Naphth-D-Trp-D-Ala-ss-Naphth-D- Phe-Val-Y (X1'-, (X2'-)a, (X3'-)b)-ss-Naphth-D-Lys-D-His-D-His-His-D-Arg Thr-Y The peptides of the instant invention can be prepared by solution methods known in the art or by using standard solid-phase techniques. The solid-phase synthesis, for example, can be commenced from the C-terminal end of the peptide using an a-amino protected amino acid. A suitable starting material can be prepared, for instance, by attaching the required a-amino acid to a chloromethyl resin, a hydroxymethyl resin, a benzhydrylamine (BHA) resin, or a p-methylbenzylhydrylamine (p-Me BHA) resin. One such chloromethyl resin is sold under the tradename BIO-BEADS SX-1 by Bio Rad Laboratories, Richmond, California. The preparation of the hydroxymethyl resin is described by Bodansky et al., Chem. Ind. (London) 38, 1597 (1966). The BHA resin has been described by Pietta and Marshall, Chem. Commn. 650 (1970) and is commercially available from Beckman Instruments, Inc., Palo Alto, California in the hydrochloride form thereof (BHA-HCl). In the solid-phase preparation of the compounds of this invention, a protected amino acid can be coupled to a resin with the aid of a coupling agent. After the initial coupling, the a-amino protecting group can be removed by a choice of reagents including trifluoroacetic acid (TFA) or hydrochloric acid (HCl) solutions in or ganic solvents at room temperature. After removal of the a-amino protecting group, the remaining protected amino acids can be coupled stepwise in the desired order. Each protected amino acid can be generally reacted in about a 3-fold excess using an appropriate carboxyl group activator such as dicyclohexylcarbodiimide (DCC) in solution, for example, in methylene chloride(CH2Cl2)-dimethylforma- mide (DMF) mixtures. After the desired amino acid sequence has been completed, the desired peptide can be cleaved from the resin support by treatment with a reagent such as hydrogen fluoride (HF) which not only cleaves the peptide from the resin, but also cleaves all remaining side-chain protecting groups. When a chloromethyl resin or hydroxymethyl resin is used, HF treatment results in the formation of the free peptide acids of formulas I-III (Y = -COOH). When the BHA or p-Me-BHA resin is used, HF treatment results directly in the free peptide amides of formulas I-III (Y = -CONH2). Alternatively, when the chloromethylated or hydroxymethyl resin is employed, the side-chain protected peptide can¯be cleaved from the resin by treatment of the peptide-resin with ammonia to give the desired side-chain protected amide or with an alkylamine to give a side-chain protected alkylamide or dialkylamide. Side-chain protection can then be removed in the usual fashion by treatment with HF to give the free peptide amides, alkylamides, or dialkylamides. In preparing the esters of this invention, the resins used to prepare the acids of formulas I-III (Y = -COOH) can be employed and the side-chain protected peptide can be cleaved with a base and an appropriate alcohol, i.e., methanol. Side-chain protecting groups can then be removed in the usual fashion by treatment with HF to obtain the desired ester. The solid-phase procedure discussed above is well known in the art and has been essentially described by Stewart and Young, Solid Phase- Peptide-Synthes-is, Freeman and Co., San Francisco (1969). Some of the well known solution methods which can be employed to synthesize the peptides of the instant invention are set forth in Bodansky et al., Peptide Synthesis, 2nd Edition, John Wiley & Sons, New York, N.Y. 1976). Accordingly, also within the scope of the instant invention are intermediate compositions prepared during the synthesis of the novel peptides of formulas I II. Intermediate compositions prepared via solid-phase techniques are the peptide-resin compounds of formulas VI-VII and intermediate compositions prepared via solution techniques are the protected peptide-compounds of formulas VIII-XIII: EMI28.1 EMI29.1 B1-B2-B3-b4-B'5-Y (x) EMI29.2 B1-B2-B3-B4-B'6-Y (XIII) wherein Pr1 is an a-amino protecting group; q, r, and s are each either 0 or 1; a and b are as defined above; m is either 0 or 1; X1iVt X2 iv, X3'V, and X1vt X2V, and x3v are selected from a group consisting of N-terminal and desamino alpha-carbon substitutions and radicals; B1 and B4 are selected from a group consisting of histidyl, arginyl, lysyl, a-naphthylalanyl, ss-naphthylalanyl, isoquinolyl, tyrosyl, tryptophyl, phenylalanyl, homologues and analogues thereof, the side-chain protected forms thereof, and, with respect to B1, the desamino forms thereof; B2, Bg, and B'5 are selected from a group consisting of D-histidyl, D-arginyl, D-lysyl, D-a-naphthylalanyl, D-B-naphthylalanyl, D-isoquinolyl, D-tyrosyl, Dtryptophyl, D-phenylalanyl, homologues and analogues thereof, the side-chain protected forms thereof, and, with respect to B'5, the descarboxy forms thereof; B3 is selected from a group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparginyl, glutaminyl, histidyl, D-alanyl, D-valyl, D-leucyl, D-isoleucyl, D-prolyl, D-seryl, D-threonyl, D-methionyl, D-aspartyl, D-glutamyl, D-asparaginyl, D-glutaminyl, D-histidyl, homologues and analogues thereof, and the side-chain protected forms thereof; B6 and B'6 are selected from a group consisting of amino acid residues of the L- and D- configuration, homologues and analogues thereof, the side-chain protection forms thereof; &commat; is a resin; Y is as defined above; and Pr2 is a carboxyl protecting group; provided that (a) when (1) a is 1 and b and m are 0 and X2iv is selected from the group consisting of -H and -CH3; (2) B1 and B4 are selected from the group consisting of tyrosyl, tryptophyl, phenylalanyl, and the side-chain protected forms thereof; (3) B3 is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparaginyl, glutaminyl, histidyl and the side-chain protected forms thereof; and, with respect to formulas (VIII) and (X), (4) Y is selected from the group consisting of -NR1R2, -OR, and CH2OR, wherein each R, R1, and R2 is selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of B2, B5, and B'5 is selected such that it is not from a group consisting of D-tyrosyl, D-tryptophyl, D-phenylalanyl, and, with respect to Bi5, the descarboxy forms thereof, and the side-chain protected forms thereof; (b) when (1) a is 1 and b and m are 0 and X2iv is selected from the group consisting of -H and -CH3; (2) B2 and B5 or B's are selected from the group consisting of D-tyrosyl, Dtryptophyl, D-phenylalanyl, and, with respect to B'5, the descarboxy forms thereof, and the side-chain protected forms thereof; (3) B3 is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparaginyl, glutaminyl, histidyl, and the side-chain protected forms thereof; and, with respect to formulas (VIII) and (X), (4) Y is selected from the group consisting of -NR1R2 -OR, and -CH20R, wherein each R, R1, and R2 is selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of B1 and B4 is selected such that it is not from a group consisting of tyrosyl, tryptophyl, phenylalanyl, and the side-chain protecte forms thereof; (c) when (1) a is 1 and b and m are 0 and X2V is selected from the group consisting of -H, -CH3, and -CHOCH3; (2) B1 and B4 are selected from the group consisting of tyrosyl, tryptophyl, phenylalanyl, and the side-chain protected forms thereof; (3) B3 is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, seryl, threonyl, methionyl, asparaginyl, glutaminyl, and the side-chain protected forms thereof; (4) B6 is selected from the group consisting of asparaginyl, glutaminyl, glutamyl, arginyl, lysyl, seryl, threonyl, and the side-chain protected forms thereof; and, with respect to formulas (XI) and (XIII), (5) Y is selected from the group consisting of -NR1R2, -OR, and -CH2ORt wherein each R, R1, and R2 is selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of B2 and B5 is selected such that it is not from a group consisting of D-tyrosyl, D-tryptophyl, D-phenylalanyl, and the side-chain protected forms thereof; and (d) when (1) a is 1 and b and m are 0 and X2v is selected from the group consisting of -H, -CH3, and -CHOCH3; (2) B2 and B5 are selected from the group consisting of D-tyrosyl, Dtryptophyl, D-phenylalanyl, and the side-chain protected forms thereof; (3) B3 is selected from the group consisting of glycyl, alanyl, valyl, leucyl, isoleucyl, prolyl, seryl, threonyl, methionyl, aspartyl, glutamyl, asparaginyl, glutaminyl, histidyl, and the side-chain protected forms thereof; (4) B6 is selected from the group consisting of asparaginyl, glutaminyl, glutamyl, arginyl, lysyl, seryl, threonyl, and the side-chain protected forms thereof; and, with respect to formulas (XI) and (XIII), (5) Y is selected from the group consisting of -NR1R2, -OR, and -CH20R, wherein each R, R1, and R2 is selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of B1 and B4 is selected such that it is not from a group consisting of tyrosyl, tryptophyl, phenylalanyl, and the side-chain protected forms thereof. Preferably, the peptide resins of formula VI, and the protected peptide-compounds of formulas VIII-X, have the amino acid sequence wherein B1 and B4 are selected from the group consisting of histidyl, tryptophyl, phenylalanyl, tyrosyl, homologues and analogues thereof, the side-chain protected forms thereof, and, with respect to B1, the desamino forms thereof; B2, Bg, and B's are selected from the group consisting of D-histidyl, Dtryptophyl, D-phenylalanyl, D-tyrosyl, homologues and analogues thereof, and, with respect to B'5, the descarboxy forms thereof, and the side-chain protected forms thereof; and B3 is selected from the group consisting of glycyl, alanyl, seryl, asparaginyl, prolyl, D-alanyl, D seryl, D-asparaginyl, D-prolyl, homologues and analogues thereof, and the side-chain protected forms thereof. Preferably, the peptide resins of formula VII, and the protected peptide-compounds of formulas XI-XIII, have the amino acid sequence wherein B1 and B4 are selected from the group consisting of histidyl, tryptophyl, phenylalanyl, tyrosyl, homologues and analogues thereof, the side-chain protected forms thereof, and, with respect to B1, the desamino forms thereof; B2 and B5 are selected from the group consisting of D-histidyl, D-tryptophyl, Dphenylalanyl, D-tyrosyl, homologues and analogues thereof, and the side-chain protected forms thereof; B3 is selected from the group consisting of glycyl, alanyl, seryl, asparaginyl, prolyl, D-alanyl, D-seryl, D-asparaginyl, D-prolyl, homologues and analogues thereof, and the side-chain protected forms thereof, and B6 and B'6 are selected from the group consisting of arginine, lysine, ornithine, histidine, aspartic acid, glutamic acid, asparagine, glutamine, D-arginine, D-lysine, D-ornithine, D-histidine, D-aspartic acid, D-glutamic acid, D-asparagine, D-glutamine, D-arginine, homologues and analogues thereof, and the descarboxy forms thereof; and, with respect to Bl6, the descarboxy forms thereof, and the side-chain protection forms thereof. More preferably, the peptide-resins of this invention are represented by formulas XIV and XV and the protected peptide-compounds are represented by formulas XVI-XXI: EMI33.1 EMI34.1 B1-D-Trp-B3-B4-B'5-Y (XVIII) EMI34.2 B1-D-Trp-B3-B4-B5-b6-O-Y (XXI) wherein B1 is selected from the group consisting of tyrosyl, O-methyltyrosyl, histidyl, 3-N-methylhistidyl, pchlorophenylalanyl, the desamino forms thereof, and the side-chain protected forms thereof; B3 is selected from the group consisting of alanyl, seryl, D-alanyl and the side-chain protected forms thereof; B4 is selected from the group consisting of tryptophyl, tyrosyl and the sidechain protected forms thereof; B5 and B'5 are selected from the group consisting of D-phenylalanyl, D-histidyl, D-tyrosyl, D-p-chlorophenyialanyl, and, with respect to B'5 the descarboxy forms thereof, and the side-chain protected forms thereof and B6 and B'6 are selected from the group consisting of arginine, homoarginine, lysine, ornithine, aspartic acid, glutamic acid, asparagine, glutamine, and D-lysine. Suitable a-amino acid protecting groups Prl, include, but are not limited to, tertiary-butyloxycarbonyl (BOC), isoamyloxycarbonyl (AOC), o-nitrophenylsulfenyl (NPS), fluoroenylmethyloxycarbonyl (FMOC), o-nitropyridinylsulfenyl (NPYS), and biphenylproploxycarbonyl (BPOC). Suitable carboxyl protecting groups, Pr2, include, but are not limited to, salts (e.g., Li+, Na+ CS+, etc.), methyl, ethyl, benzyl, benzhydryl, substituted benzyl, phthalimidomethyl, tertiary butyl, phenacyl, phenyl, 4-picolyl, 2-methylthioethyl, 2(p-toluenesulfonyl)ethyl, 2(p-nitrothiophenyl)ethyl, p-methylthiophenyl, and hydrazides. In addition to the resins, &commat;, noted above, other resins include, but are not limited to, phenylacetamidomethyl (PAM), chloromethyl, and poly-N-acrylpyrrolidine resins. Virtually any suitable N-terminal and desamino alpha-carbon substitution and radical can be used in the instant invention. Typical N-terminal and dex amino alpha-carbon substitutions and radicals include, but are not limited to, those set forth in Table V. TABELE V N-Terminus ond Desamino Substitutions and RadicalsÚ EMI37.1 X1 <SEP> X'2 <SEP> X'3 <SEP> o <SEP> b <SEP> m <SEP> q <SEP> r <SEP> s <tb> <SEP> N-Terminus <SEP> Substitutions <SEP> and <SEP> Radicals <tb> R1-(R1#H) <SEP> R2-(R2#H) <SEP> - <SEP> 1 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 0 <tb> - <SEP> R2- <SEP> - <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 0 <tb> R1-(R1#H) <SEP> R2-(R2#H) <SEP> R3-(R3#H) <SEP> 1 <SEP> 1 <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 0 <tb> R1- <SEP> R2- <SEP> R3- <SEP> 1 <SEP> 1 <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 0 <tb> <SEP> O <tb> <SEP> # <tb> R1-Z-C- <SEP> R2- <SEP> - <SEP> 1 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 0 <tb> <SEP> O <tb> <SEP> # <tb> R1-C- <SEP> R2- <SEP> - <SEP> 1 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 0 <tb> R1- <SEP> -0- <SEP> - <SEP> 1 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 1 <SEP> 0 <tb> <SEP> R2 <tb> <SEP> # <tb> R1-N-(R1 & 2#H) <SEP> R3-(R3#H) <SEP> - <SEP> 1 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 0 <tb> R2 <tb> # <tb> R1-N-(R1 & 2#H) <SEP> - <SEP> - <SEP> 0 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 1 <SEP> 0 <tb> TABLE V(contd.) EMI38.1 X'1 <SEP> X'2 <SEP> X'3 <SEP> a <SEP> b <SEP> m <SEP> q <SEP> r <SEP> s <tb> <SEP> R2 <tb> <SEP> # <tb> -N- <SEP> - <SEP> - <SEP> 0 <SEP> 0 <SEP> 1 <SEP> 1 <SEP> 1 <SEP> 0 <tb> <SEP> R2 <tb> <SEP> # <tb> -N- <SEP> R3-(R30H) <SEP> - <SEP> 1 <SEP> 0 <SEP> 1 <SEP> 1 <SEP> 0 <SEP> 0 <tb> <SEP> R2 <SEP> Z <tb> <SEP> # <SEP> # <tb> R1-N-C-(R1 & 2#H) <SEP> R3-(R3#H) <SEP> - <SEP> 1 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 0 <tb> <SEP> R2 <SEP> Z <tb> <SEP> # <SEP> # <tb> R1-N-C-(R1 & 2#H) <SEP> - <SEP> - <SEP> 0 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 1 <SEP> 0 <tb> R2 <SEP> Z <tb> <SEP> # <SEP> # <tb> -N-C- <SEP> R3-(R3#H) <SEP> - <SEP> 1 <SEP> 0 <SEP> 1 <SEP> ^ <SEP> 0 <SEP> 0 <tb> <SEP> Desamino <SEP> Substituents <SEP> and <SEP> Radicals <tb> R- <SEP> - <SEP> - <SEP> 0 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 0 <tb> Rz-(R#Z) <SEP> - <SEP> - <SEP> 0 <SEP> 0 <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 0 <tb> -Z- <SEP> - <SEP> - <SEP> 0 <SEP> 0 <SEP> 1 <SEP> 1 <SEP> 0 <SEP> 0 <tb> 1. LEGEND: R, R1, R2, R3 and Z are as defined in TABLE I, supra. The growth hormone releasing peptides of formulas I and II and combinations thereof (including combinations of formula III) with at least one growth promoting agent are useful in-vitro as unique tools for understanding how growth hormone secretion is regulated at the pituitary level. This includes use in the evaluation of many factors thought or known to influence growth hormone secretin such as age, sex, nutritional factors, glucose, amino acids, fatty acids, as well as fasting and non-fasting states. In addition, the peptides of this invention can be used in the evaluation of how other hormones modify growth hormone releasing activity. For example, it has already been established that somatostatin inhibits growth hormone release. Other hormones that are important and in need of study as to their effect on growth hormone release include the gonadal hormones, e.g., testosterone, estradiol, and progesterone; the adrenal hormones, e.g., cortisol and other corticoids, epinephrine and norepinephrine; the pancreatic and gastrointestinal hormones, e.g., insulin, glucagon, gastrin, secretin; the vasoactive intestinal peptides, e.g., bombesin; and the thyroid hormones, e.g., thyroxine and triiodothyronine. These peptides and combinations of this invention can also be employed to investigate the possible negative or. positive feedback effects of some of the pituitary hormones, e.g., growth hormone and endorphin peptides, on the pituitary to modify growth hormone release. Of particular scientific importance is the use of these peptides to elucidate the subcellular mechanisms mediating the release of growth hormone. The peptides and combinations of this invention can also be administered to animals, including man, to release growth hormone in vivo. For example, the peptides can be administered to commercially important animals such as swine, cattle, sheep and the like to accelerate and increase their rate and extent of growth, and to increase milk production in such animals. In addition, these peptides can be administered to humans in vtvo as a diagnostic tool to directly determine whether the pituitary is capable of releasing growth hormone. For example, the peptides and combinations can be administered in--vivo to children. Serum samples taken before and after such administration can be assayed for growth hormone. Comparison of the amounts of growth hormone in each of these samples would be a means for directly determining the ability of the patient's pituitary to release growth hormone. Accordingly, the present invention includes within its scope pharmaceutical compositions comprising, as an active ingredient, at least one of the peptides or combinations of this invention in association with a pharmaceutical carrier or diluent. Optionally, the active ingredient of the pharmaceutical eompostions can comprise a growth promoting agent in addition to at least one of the peptides of formulas I or II or another composition which exhibits a different activity, e.g., an tibiotic or other pharmaceutically active material. Growth promoting agents include, but are not limited to, TRH, diethylstilbesterol, theophylline, enkephalins, E series prostaglandins, compounds disclosed in U.S. Patent 3,239,345, e.g., zeranol, and compounds disclosed in U.S. Patent 4,036,979, e.g., sulbenox. The peptides of this invention can be administered by oral, parenteral (e.g., intramuscular, intraperitoneal, intravenous or subcutaneous injection, or implant), nasal, vaginal, rectal, sublingual, or topical routes of administration and can be formulated in dosage forms appropriate for each route of administration. Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is admixed with at least one inert pharmaceutically acceptable carrier such as sucrose, lactose, or starch. Such dosage forms can also comprise, as is normal practice, additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, the elixirs containing inert diluents commonly used in the art, such as water. Besides such inert diluents, compositions can also include adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring, and perfuming agents. Preparations according to this invention for parenteral administration include sterile aqueous or nonaqueous solutions, suspensions, or emulsions. Examples of non-aqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils, such as olive oil and corn oil, gelatin, and injectable organic esters such as ethyl oleate. Such dosage forms may also contain adjuvants such as preserving, wetting, emulsifying, and dispersing agents. They may be sterilized by, for example, by filtration through a bacteria-retaining filter, by incorporating sterilizing agents into the compositions, by irradiating the compositions, or by heating the compositions. They can also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use. Compositions for rectal or vaginal administration are preferably suppositories which may contain, in addition to the active substance, excipients such as cocoa butter or a suppository wax. Compositions for nasal or sublingual administration are also prepared with standard excipients well known in the art. The dosage of each active ingredient in the compositions of this invention may be varied; however, it is necessary that the amount of the active ingredient be such that a suitable doage form is obtained. The selected dosage depends upon the desired therapeutic effect, on the route of administration, and on the duration of the treatment. Generally, dosage levels per active ingredient of between 0.001 to 10 mg/kg. of body weight daily are administered to animals, e.g., mammals, to obtain effective release of growth hormone. The following examples are provided for the purpose of further illustration only and are not intended to be limitations on the disclosed invention. Example 1 Synthesis of H2-His-D-'krp-Ala-Trp-D-Phe-NHZ Para-methylbenzhydrylamine hydrochloride (p-Me BHA.HCl) resin was placed in a reaction vessel. The following procedure, starting at step 6, was then employed in conjunction with a Beckman brand Peptide Synthesizer Model No. 990 in preparing the peptide H2 His-D-Trp-Ala-Trp-D-Phe-NH2. The synthesis was started at step 6 because there was no amino acid present in the resin and one need only neutralize the resin which was initially in the HCl form. 1. Wash with methylene chloride (cH2cl2) for 1.5 minutes, three times. 2. Treat with trifluoroacetic acid - methylene chloride (40% TFA/CH2Cl2, V/V) containing 0.1% indole for 1.5 minutes. 3. Repeat Step 2 for 20 minutes. 4. Wash with chloroform (CHC13) for 1.5 minutes, three times. 5. Wash with 30% ethanol-methylene chloride (30% EtOH/CH2C12r V/V) for 1.5 minutes, two times. 6. Wash with CH2Cl2 for 1.5 minutes, three times. 7. Treat with 10% triethylamine in CH2Cl2 (10% TEA/CH2Cl2 V/V) for 1.5 minutes. 8. Repeat Step 7 for 10 minutes. 9. Wash with CH2Cl2 for 1.5 minutes, three times. 10. Add to the washed resin 2.5 equivalents of the appropriate protected amino acid in dimethyl formamidemethylene chloride (DMF-CH2Cl2). 11. Add 0.5N dicyclohexylcarbodiimide in CH2Cl2 (DCC/CH2Cl2); more than 2.5 equivalents. 12. Rinse addition funnel with CH2Cl2 and add rinse to the reaction vessel. 13. Stir the reagents in Steps 10-12 for 2 hours or more. 14. Wash with CH2Cl2 for 1.5 minutes, three times. 15. Wash with DMF for 1.5 minutes. 16. Wash with CH2Cl2 for 1.5 minutes, two times. 17. Test by ninhydrin reaction according to the procedure of Kaiser et al., Annal. Biochem., 34:595 (1970). 18. If Step 17 shows complete reaction, repeat the above procedures starting from Step 1 employing the next protected amino acid. If Step 17 shows incomplete reaction, repeat Steps 7-17. The above procedure was employed using the following sequence of amino acids: Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-His(Tos*) *Tos denotes p-toluenesulfonyl. After completion of the synthesis of the desired peptide resin, the reaction vessel containing the peptide resin was then placed in a dessicator and dried overnight under a vacuum. The dried peptide resin was removed from the reaction vessel and placed in another vessel suitable for HF cleavage. This later vessel also contained a magnetic stirring bar. A quantity of anisole sufficient to wet the peptide resin was added to this vessel. The vessel was next connected to an HF line and placed under a vacuum to remove any air therein. The vessel was then cooled to about -78 C. with a dry iceacetone bath. Doubly distilled HF (about 10 ml/gm of peptide resin) was added to the vessel. The dry iceacetone bath was then removed from the vessel and replaced by an ice-water bath. The vessel's contents were vigorously stirred for about 45 minutes while the vessel remained immersed in the ice-water bath. Most of the HF in the vessel was then removed by water aspiration. After the majority of HF was removed by water aspiration, the remaining HF and anisole were removed via a vacuum pump. The vessel's contents were washed with about 100 ml of ether to further remove any residual anisole. The peptide was removed from the resin by extraction with aqueous acetic acid (aq0HOAc). The aq'HOAc was lyophilized off to yield a fluffy peptide powder. The peptide was then purified by partition chromatography or counter current distribution (CCD) employing a butanol:HOAc:water (4:1:5) system. When further purification was necessary, a Pharmacia LH-20 brand chromatography column was also employed. Ex amp-l e 2 Synthests of H2-Tyr-D-Trp-Ala-Trp-D-His-NH2 The procedure set forth in Example 1 can be employed to synthesize the peptide H2-Tyr-D-Trp-Ala-Trp- D-His-NH2 employing the following sequence of amino acids: Boc-D-His(Tos) Boc-Trp - Boc-Ala Boc-D-Trp Boc-Tyr(BrZ*) *BrZ denotes o-bromobenzyloxycarbonyl Example 3 Synthesis of H2-His-D-Trp-Ala-Trp-D-Tyr-NH2 The procedure set forth in Example 1 can be employed to synthesize the peptide H2-His-D-Trp-Ala-Trp D-Tyr-NH2 employing the following sequence of amino acids: : Boc-D-Tyr (BrZ) Boc-Trp Boc-Ala Boc-D-Trp Boc-His (Tos) Example -4 Synthesis of H2-His-D-Trp-Ala-Trp-D-His-NH2 The procedure set forth in Example 1 can be employed to synthesize the peptide H2-His-D-Trp-Ala-Trp D-His-NH2 employing the following sequence of amino acids: Boc-D-His (Tos) Boc-Trp Boc-Ala Boc-D-Trp Boc-His (Tos) Example -5 Synthesis of H2-Tyr-D-Trp-Ala-Trp-D-p-Cl-Phe-NH2 The procedure set forth in Example 1 can be employed to synthesize the peptide H2-Tyr-D-Trp-Ala-Trp D-p-Cl-Phe-NH2 employing the following sequence of amino acids: : Boc-D-p-Cl-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-Tyr(BrZ) Example 6 Synthesis of H2-Tyr-D-Try-D-Rla-Trp-D-Phe-NH2 The procedure set forth in Example 1 can be employed to synthesize the peptide H2-Tyr-D-Trp-D-Ala Trp-D-Phe-NH2 employing the following sequence of amino acids: Boc-D-Phe Boc-Trp Boc-D-Ala Boc-D-Trp Boc-Tyr(BrZ) Example 7 Synthesis of H2-p-Cl-Phe-D-Trp-Ala-Trp-D-Phe-NH2 The procedure set forth in Example 1 can be employed to synthesize the peptide H2-p-Cl-Phe-D-Trp-Ala- Trp-D-Phe-NH2 employing the following sequence of amino acids: : Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-p-Cl-Phe Example- S Synthesis of H-desaminoTyr-D-Trp-Ala-Trp-D-Phe-NH2 The procedure set forth in Example 1 can be employed to synthesize the peptide H-desaminoTyr-D-Trp Ala-Trp-D-Phe-NH2 employing the following sequence of amino acids: Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp 3(p-OH-phenyl)propanoic acid Eample- 9 EMI48.1 The procedure set forth in Example 1 can be employed with several modifications to synthesize the peptide H CH3CO-Tyr-D-Trp-Ala-Trp-D-Phe-NH2 employing the following sequence of amino acids: Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-Tyr(BrZ) The modifications consisted of the following additional steps after the last protected amino acid, Boc-Tyr(BrZ) was added to the peptide resin: 19. The Boc group was removed from the peptide resin by TFA. 20. The resulting peptide resin was washed with CH2Cl2 for 1.5 minutes, two times. 21. Acetic anhydride (2.5 molar excess) and 2.5 molar excess of pyridine were added and stirred for about 10 minutes. 22. Repeat Step 20. The same drying and purification steps as used in Example 1 were then employed to obtain the desired peptide. Example 10 S.ynthesis..of H-o-Me-Tyo-D--Trp-Ala-Trp-D-Phe-NH2 The procedure set forth in Example 1 can be employed to synthesize the peptide H2-O-Me-Tyr-D-Trp-Ala- Trp-D-phe-NH2 employing the following sequence of amino acids: Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-O-Me-Tyr(BrZ) Example 1-1 Synthesis of H2-Tyr-D-Trp-Ala-Trp-D-Phe-Met-NH2 BHA*HCl resin was placed in a reaction vessel. The following procedure was then employed in conjunction with a Beckman brand Peptide Synthesizer Model No. 990 in preparing the hexapeptide H2-Tyr-D-Trp-Ala Trp-D-Phe-Met-NH2: 1. Methylene chloride (CHzCl2; about 10 ml/gm of BHA*HCl resin) was added to the reaction vessel. The BHA'- HCl resin was washed with vigorous stirring for about 1.5 minutes. The CH2Cl2 solution was then drained from the reaction vessel. This washing step was repeated once. 2. A triethylamine solution ((Et3N)/CH2Cl2 (10:90); about 10 ml/gm BHA-HCl resin) was added to the washed BHA.HCl resin in the reaction vessel. The resulting mixture was vigorously stirred for about 1.5 minutes. The solution was then drained from th reaction vessel. 3. Another Et3N/CH2Cl2 (10:90) solution (about 10 ml/gm BHA.HCl) was added to the reaction vessel. The BHA*- HCl resin was neutralized by vigorous stirring for about 20 minutes. The solution was then drained from the reaction vessel. 4. CH2Cl2 (about 10 ml/gm of BHA.HCl resin) was added to the reaction vessel. The resulting mixture was vigorously stirred for about 1.5 minutes. The solution was then drained from the reaction vessel. This procedure was repeated an additional two times. 5. Tertiarybutyloxycarbonyl-methionine (Boc-Met; about 2.5 times the theoretical amount of the total binding capacity of the BHA HCl resin originally placed in the reaction vessel) in about 50 ml of dimethylformamidemethylene chloride solution (DMF-CH2cl2 (1:9)) was added to the reaction vessel. The resulting mixture was vigorously stirred for about 1.5 minutes. 6. A 0.5 molar (M) dicyclohexylcarbodiimide (DCC) in CH2Cl2 solution (about 2.5 times the theoretical amount of total binding capacity of the BHA-HCl resin originally placed in the reaction vessel) was added to the reaction vessel. The resulting mixture was vigorously stirred until a negative ninhydrin test was obtained (about 120 minutes). The solution was then drained from the reaction vessel. 7. CH2Cl2 (about 10 ml/gm of BHA-HCl resin) was added to the reaction vessel. The resulting solution was vigorously stirred for about 1.5 minutes. The solution was then drained from the reaction vessel. This washing procedure was repeated once. 8. DMF (about 10 ml/gm of BHA.HCl resin) was added to the reaction vessel. The resulting mixture was stirred for about 1.5 minutes. The solution was then drained from the reaction vessel. 9. CH2Cl2 (about 10 ml/gm of BHA.HCl resin) was added to the reaction vessel. The resulting mixture was vigorously stirred for about 1.5 minutes. The solution was then drained from the reaction vessel. This washing procedure was repeated an additional two times. 10. A trifluoroacetic acid/methylene chloride solution (TFA/CH2Cl2 (40:60); about 10 ml/gm of BHAHCl resin) was added to the reaction vessel. The resulting mixture was vigorously stirred for about 1.5 minutes. The solution was then drained from the reaction vessel. 11. Another TFA/CH2Cl2 (40:60) solution (about 10 ml/gm of BHA.HCl resin) was added to the reaction vessel. The resulting mixture was vigorously stirred for about 20 minutes. The solution was then drained from the reaction vessel. 12. CH2Cl2 (about 10 ml/gm of BHA.HCl resin) was added to the reaction vessel. The resulting solution was vigorously stirred for about 1.5 minutes. The solution was then drained from the reaction vessel. This washing procedure was repeated once. 13. A triethylamine solution ((Et3N)/CH2Cl2 (10:90); about 10 ml/gm BHA HCl resin) was added to the washed BHAHCl resin in the reaction vessel. The resulting mixture was vigorously stirred for about 1.5 minutes. The solution was then drained from the reaction vessel. 14. Another Et3N/CH2Cl2 (10:90) solution (about 10 ml/gm BHA.HCl) was added to the reaction vessel. The BHA.- HCl resin was neutralized by vigorous stirring for about 20 minutes. The solution was then drained from the reaction vessel. 15. Chloroform (CHC13; about 10 ml/gm of BHA.HCl resin) was added to the reaction vessel. The resulting mixture was vigorously stirred for about 1.5 minutes. The solution was then drained from the reaction vessel. 16. An ethanol/methylene chloride solution (EtOH/CH2Cl2 (30:70); about 10 ml/gm of BHA-HCl resin) was added to the reaction vessel. The resulting mixture was vigorously stirred for about 1.5 minutes. The solution was then drained from the reaction vessel. This washing step was repeated once. Steps 4 through 16 were then repeated employing the following sequence of amino acids: Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-Tyr (BrZ*) *BrZ denotes o-bromobenzyloxycarbonyl After completion of the synthesis of the desired peptide resin, the reaction vessel containing the peptide resin was then placed in a dessicator and dried overnight under a vacuum. The dried peptide resin was removed from the reaction vessel and placed in another vessel suitable for HF cleavage. This latter vessel also contained a magnetic stirring bar. A quantity of anisole sufficient to wet the peptide resin was added to this vessel. The vessel was next connected to an HF and placed under a vacuum to remove any air therein. The vessel was then cooled to about -78 C. with a dry iceacetone bath. Doubly distilled HF (about 10-ml/gm of peptide resin) was added to the vessel. The dry iceace tone bath was then removed from the vessel and replaced by an ice-water bath. The vessel's contents were vigorously stirred for about 45 minutes while the vessel remained immersed in the ice-water bath. Most of the HF in the vessel was then removed by water aspiration, the remaining HF and anisole were removed via a vacuum pump. The vessel's contents were washed with about 100 ml of ether to further remove any residual anisole. The peptide was removed from the resin by extraction with 30% aqueous acetic acid (aq.HOAc). The aq.HOAc was lyophilized off to yield a fluffy peptide powder. The peptide was then purified by partition chromatography or counter current distribution (CCD) employing a butanol: HOAc: water (4:1:5) system. When further purification was necessary, a Pharmacia LH-20 brand chromatography column was also employed. Example 12 Synthesis of H2-Tyr-D-Trp-Ala-Trp-D-Phe-Thr-NH2 The procedure set forth in Example 11 was employed to synthesize the hexapeptide H2-Tyr-D-Trp-Ala Trp-D-Phe-Thr-NH2 employinq the following sequence of amino acids: Boc-Thr(Bzl*) Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-Tyr(BrZ) *Bzl denotes benzyl. Example 13 Synthesis of H2-Tyr-D-Trp-Ala-Trp-D-Phe-Gln-OH The procedure set forth in Example 11 was employed to synthesize the hexapeptide H2-Tyr-D-Trp-Ala- Trp-D-Phe-Gln-OH employing the following sequence of amino acids: Boc-Glu-a-benzyl ester Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-Tyr(BrZ) Example - 1-4 Synthesis of H2-Tyr-D-Trp-Ala-Trp-D-Phe-Gln-NH2 The procedure set forth in Example 11 was employed with several modifications to synthesize the hexapeptide H2-Tyr-D-Trp-Ala-Trp-D-Phe-Gln-NH2. The modifications consisted of: (1) Omitting steps 2-4 of Example 11 and replacing them with a single step which entailed dissolving Boc-Gln (about 5 times the theoretical amount of the total binding of the BHA.HCl resin originally placed in the reaction vessel) in 10 ml of CH3Cl2-DMF solution (3:2) present in a round bottom flask. The flask and its contents was cooled in ice and then DCC (about 1.25 times the theoretical amount of the total binding capacity of the BHA.HCl resin originally placed in the reaction vessel) was added to the flask. The resulting mixture was stirred in an ice bath for about 25-30 minutes. The DCC urea precipitate formed by the reaction between Boc-Gln and DCC was separated from the supernatant via filtration. The supernature comprising the CH2Cl2-DMF solution having a symmetrical anhydride (also formed by the reaction between Boc-Gln and DCC) dissolved therein was added to the reaction vessel. The resulting mixture was stirred until a negative ninhydrin test was obtained. The solution was then drained from the reaction vessel. (2) After completing steps 7 through 16 of Example 11, steps 4 through 16 of Example 11 were then repeated, without modification, employing the following sequence of amino acids: Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-Tyr(BrZ) Eamp-le-1-5 Synthesis of H2-Tyr-D-Trp-Ala-Trp-D-Phe-Asn-NH2 The procedure set forth in Example 11 was employed with several modifications to synthesize the hexapeptide H2-Tyr-D-Trp-Ala-Trp-D-Phe-Asn-NH2. The modifications consisted of: (1) Omitting steps 2-4 of Example 11 and replacing them with a simple step whic entailed dissolving Boc-Asn (about 5 times the theoretical amount of the total binding capacity of the BHA.HCl resin originally placed in the reaction vessel) in about 50 ml of DMF in a suitable flask. The resulting solution was added to the reaction vessel to form a mixture. The mixture was vigorously stirred until a negative ninhydrin test was obtained. The solution was then drained from the reaction vessel. (2) After completing steps 7 through 16 of Eample 11, steps 4 through 16 of Example 11 were then repeated, without modification, employing the following sequence of amino acids: Boc-D-Phe Boc-Trp Boc-Ala Boc-Tyr(BrZ) Example 16 Synthesis of H2-His-D-Trp-D-Phe-Lys-NH Para-methylbenzhydrylamine hydrochloride (p-Me BHA.HCl) resin was placed in a reaction vessel. The following procedure, starting at step 6, was then employed in conjunction with a Beckman brand Peptide Synthesizer Model 990 in preparing the peptide H2-His-D Trp-Ala-Trp-D-Phe-Lys-NH2. The synthesis was started at step 6 because there was no amino acid present in the resin and one need only neutralize the resin which was initially in the HCl form. 1. Wash with methylene chloride (CH2cl2) for 1.5 minutes, three times. 2. Treat with trifluoroacetic acid -- methylene chloride (40% TFA/CH2Cl2, V/V) containing 0.1% indole for 1.5 minutes. 3. Repeat Step 2 for 20 minutes. 4. Wash with chloroform (CHC13) for 1.5 minutes, three times. 5. Wash with 30% ethanol-methylene chloride (30% EtOH/CH2C12r V/V) for 1.5 minutes, two times. 6. Wash with CH2Cl2 for 1.5 minutes, three times. 7. Treat with 10% triethylamine in CH2Cl2 (10% TEA/CH2Cl2, V/V) for 1.5 minutes. 8. Repeat Step 7 for 10 minutes. 9. Wash with CH2Cl2 for 1.5 minutes, three times. 10. Add to the washed resin 2.5 equivalents of the appropriate protected amino acid in dimethyl formamidemethylene chloride (DMF-CH2Cl2). 11. Add 0.5N dicyclohexylcarbodiimide in CH2Cl2 (DCC/CH2Cl2); more than 2.5 equivalents. 12. Rinse addition funnel with CH2Cl2 and add rinse to the reaction vessel. 13. Stir the reagents in Steps 10-12 for 2 hours or more. 14. Wash with CH2Cl2 for 1.5 minutes, three times. 15. Wash with DMF for 1.5 minutes. 16. Wash with CH2Cl2 for 1.5 minutes, two times. 17. Test by ninhydrin reaction according to the procedure of Kaiser et al., Annal. Bloch-em., 3-4:595 (1970). 18. If Step 17 shows complete reaction, repeat the above procedures starting from Step 1 employing the next protected amino acid. If Step 17 shows incomplete reaction, repeat Steps 7-17. The above procedure was employed using the following sequence of amino acids: Bo'c-Lys(ClZ+) Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-His(Tos*) +ClZ denotes o-chloro-benzyloxycarbonyl. *Tos denotes p-toluenesulfonyl. After completion of the synthesis of the desired peptide resin, the reaction vessel containing the peptide resin was then placed in a dessicator and dried overnight under a vacuum. The dried peptide resin was removed from the reaction vessel and placed in another vessel suitable for HF cleavage. This latter vessel also contained a magnetic stirring bar. A quantity of anisole sufficient to wet the peptide resin was added to this vessel. The vessel was next connected to an HF line and placed under a vacuum to remove any air therein. The vessel was then cooled to about -78 C. with a dry iceacetone bath. Doubly distilled HF (about 10 ml/gm of peptide resin) was added to the vessel. The dry iceacetone bath was then removed from the vessel and replaced by an ice-water bath. The vessel's contents were vigorously stirred for about 45 minutes while the vessel remained immersed in the ice-water bath. Most of the HF in the vessel was then removed by water aspiration. After the majority of HF was removed by water aspiration, the remaining HF and anisole were removed via a vacuum pump. The vessel's contents were washed with about 100 ml of ether to further remove any residual anisole. The peptide was removed from the resin by extraction with aqueous acetic acid (aq.HOAc). The aq.HOAc was lyophilized off to yield a fluffy peptide powder. The peptide was then purified by partition chromatography or counter current distribution (CCD) employing a butanol:HOAc:water (4:1:5) system. When further purification was necessary, a Pharmacia LH-20 brand chromatography column was also employed. Example -17 Synthesis- of - H --Tqr-D-Trp-Al a-Trp-D-Phe-Ly s--N The procedure set forth in Example 16 can be employed to synthesize the peptide H2-Tyr-D-Trp-Ala-Trp- D-Phe-Lys-NH2 employing the following sequence of amino acids: Boc-Lys(ClZ) Boc-D- Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-Tyr(BrZ*) *BrZ denotes o-bromobenzyloxycarbonyl Example--18 Systhesis of H2-Tyr-D-Trp-Ala-Trp-D-Phe-Glu-NH2 The procedure set forth in Example 16 can be employed to synthesize the peptide H2-Tyr-D-Trp-Ala-Trp- D-Phe-Glu-NH2 employing the following sequence of amino acids: : Boc-Glu-y-Bzl* Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-Tyr(BrZ) *y-Bzl denotes y-benzyl ester ExampIe- 19 Synthesis of H2-Tyr-D-Trp-Ala-Trp-D-Phe-Phe-NH2 The procedure set forth in Example 16 can be employed to synthesize the peptide H2-Tyr-D-Trp-Ala-Trp- D-Phe-Phe-NH2 employing the following sequence of amino acids: Boc-Phe Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-Tyr(BrZ) Example 20 Synthesis of H2-Tyr-D-Trp-Gly-Trp-D-Phe-Gln-NH The procedure set forth in Example 16 can be employed with one modification to synthesize the peptide H2-Tyr-D-Trp-Gly-Trp-D-Phe-Gln-NH2 employing the following sequence of amino acids: Boc-Gln-ONP* Boc-D-Phe Boc-Trp Boc-Gly Boc-D-Trp Boc-Tyr(BrZ) *ONP denote p-nitrophenyl ester. The sole modification was made just in the procedure for coupling Boc-Gln-ONP to the resin. This modification consisted of the omission of step 11 of Example 16 in this one coupling procedure. Example 21 Synthesis of H2-His-D-Trp-Ala-Trp-D-phe-Lys-oH The procedure set forth in Example 16 can be employed with several modifications to synthesize the peptide H2-His-D-Trp-Ala-Trp-D-phe-Lys-oH employing the following sequence of amino acids: Boc-Lys(ClZ) Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-His(Tos) The modifications were as follows: 1. A hydroxymethyl resin was employed instead of the p-ME-BHA*HCl resin. 2. Steps 6-18 were modified as follows just in the procedure for coupling Boc-Lys(ClZ) to the hydroxymethyl resin: a. Step 6 was the same; b. Steps 7 through 9 were omitted; c. Steps 10 and 11 were the same; d. Step 12 was omitted and the following procedure was substituted therefor: Add 2.5 equivalents of N,N-dimethylaminopyridine (DMAP). e. Steps 13 through 16 were the same; f. Steps 17 and 18 were omitted and the following procedure was substituted therefor: Dry the amino acid-resin under vacuum until a constant weight is obtained. If the final constant weight is equal to the sum of the weights of the resin and Bocamino acid added to the reaction vessel, then add 10 equivalents of. benzoyl chloride and 10 equivalents of pyridine to deactivate any unused hydroxymethyl resin. Wash as set forth in steps 15 and 16. Then employ steps 1-18 of Example 16 for remaining protected amino acids. If the final constant weight is not equal to the sum of the weights of the resin and Boc-amino acid added to the reaction vessel, then repeat steps 10 to end as modified above in this example. Example 22 Synthesis of H2-His-D-Trp-Ala-Trp-D-phe-Arg-NH2 The procedure set forth in Example 16 can be employed to synthesize the peptide H2-His-D-Trp-Ala-Trp- D-Phe-Arg-NH2 employing the following sequence of amino acids: Aoc*-Arg(Tos) Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-His(Tos) *Aoc denotes isoamyloxycarbonyl Example 23 Synthesis of H2-His-D-Trp-Ala-Trp-D-Phe-Gln-NH2 The procedure set forth in Example 16 can be employed with one modifcation to synthesize the peptide H2-His-D-Trp-Ala-Trp-D-Phe-Gln-NH2 employing the following sequence of amino acids: Boc-Gln-ONP Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-His(Tos) The sole modification was made first in the procedure for coupling Boc-Gln-ONP to the resin. This modification consisted of the omission of step 11 of Example 16 in this one coupling procedure. Example 24 Synthesis of H2-His-D-Trp-Ala-Trp-D-Phe-lu-NH2 The procedure set forth in Example 16 can be employed to synthesize the peptide H2-His-D-Trp-Ala-Trp- D-Phe-Glu-NH2 employing the following sequence of amino acids: Boc-Glu-y-Bzl Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-His(Tos) Example 25 Synthesis of H2-His-D-Trp-Ala-Trp-D-phe-HomoArg-NH2 The procedure set forth in Example 16 can be employed to synthesize the peptide H2-His-D-Trp-Ala-Trp- D-Phe-HomoArg-NH2 employing the following sequence of amino acids: : Boc-HomoArg(Tos) Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-His(Tos) Example 26 Synthesis of H2-3-N-Me-His-D-Trp-Ala-Trp-D-phe-Lys-NH2 The procedure set forth in Example 16 can be employed to synthesize the peptide H2-3-N-Me-His-D-Trp Ala-Trp-D-Phe-Lys-NH2 employing the following sequence of amino acids: Boc-Lys(ClZ) Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-3-N-Me-His Example 27 Synthesis of H2-Hi.s-D-Trp-Ala-Trp-D-Phe-Lys-NHCH2CH3 The procedure set forth in Example 16 can be employed with several modifications to synthesize the peptide H2-His-D-Trp-D-Ala-Trp-D-Phe-Lys-NHCH2CH employing the following sequence of amino acids: : Boc-Lys(ClZ) Boc-D-Phe Boc-Trp Boc-D-Ala Boc-D-Trp Boc-His(Tos) The following ethylamine (CH3cH2NH2) cleavage procedure was employed in place of the HF cleavage procedure of Example 16: After completion of the synthesis of the desired peptide resin, the reaction vessel containing the peptide resin was then placed in a dessicator and dried overnight under a vacuum. The dried peptide resin was removed from the reaction vessel and placed in another vessel suitable for ethylamine cleavage. This latter vessel also contained a magnetic stirring bar. The vessel was placed in an ice bath and gaseous ethylamine was condensed into the vessel. The contents of the vessel was stirred overnight. This cleavage procedure was then followed by the extraction and purifications procedures as set forth in Example 16. Example 28 Synthesis of HZ-His-D-Trp-Ala-Trp-D-Phe-Orn-NH2 The procedure set forth in Example 16 can be employed to synthesize the peptide H2-His-D-Trp-Ala-Trp- D-Phe-Orn-NH2 employing the following sequence of amino acids: Boc-Orn ( Z*) Boc-D-Phe Boc-Trp Boc-Ala Boc-D-Trp Boc-His (Tos) *Z denotes benzyloxycarbonyl Example 29 Synthesis of H2-His-D-Trp-Val-Trp-D-Phe-Lys-NH2 The procedure set forth in Example 16 can be employed to synthesize the peptide H2-His-D-Trp-Val-Trp- D-Phe-Lys-NH2 employing the following sequence of amino acids: : Boc-Lys(ClZ) Boc-D-Phe Boc-Trp Boc-Val Boc-D-Trp Boc-His(Tos) Example 30 Synthesis.of HZ-is-D-Trp-Ser-Trp-D-Phe-Lys-NH2 The procedure set forth in Example 16 can be employed to synthesize the peptide H2-His-D-Trp-ser-Tr D-Phe-NH2 employing the following sequence of amino acids: Boc-Lys(ClZ) Boc-D-Phe Boc-Trp Boc-Ser(Bzl) Boc-D-Trp Boc-His(Tos) Example 31 In Vitro Growth Hormone Release Study Female rats of the CD-1 strain were housed in a constant temperature room at 24 C. with 14 hours light and 10 hours darkness. The rats were fed Purina brand rat chow ab libitum. All studies were started between 0800 and 1000 hours. Pituitaries were removed from 20 day old female rats. In each polytetrafluoroethylene beaker (10 ml) was incubated two pituitaries at 36"C. in 1 ml of lactated Ringer's solution in a Dubnoff Shaker (90 cycles/min.). Three beakers were emplyed for each dosage shown in Table VI. All medium in each beaker was removed each hour (e.g., P1, P2, 13, I4, Ig) and then fresh medium was added back to each beaker. Each medium removed was assayed for GH, in duplicate, by a standard radioimmunoassay (RIA). The growth hormone agonist of Example 1 was not added to the incubation mediums employed during the first hour of the incubation period (P1) or to the incubation mediums employed during the second hour of the incubation period (P2). The growth hormone agonist of Example 1 was dissolved in dimethylsulfoxide (DMSO; 10:1, agonist: :DMSO), added to each incubation medium employed during the third hour of the incubation period (I3), to each medium employed during the third hour of the incubation period (I3), to each medium employed during the fourth hour of the incubation period (I4) and, when performed, to each medium employed during the fifth hour of the incubation period (it). The release of growth hormone was recorded as AGH values obtained from the three beakers per doage level measured at I3, I4, and, when performed, Is are set forth in Table VI. Example 32 In Vitro Growth Hormone Releae Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 2 and the results therefrom are set forth in Table VII. Example 33 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in-vitro growth hormone release study of the peptide of Example 3 and the results therefrom are set forth in Table VIII. Example 34 In-Vitro Growth Release Study The procedure set forth in Example 31 was employed in an in-vitro growth hormone release study of the peptide of Example 4 and the results therefrom are set forth in Table IX. Example 35 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 5 and the results therefrqm are set forth in Table X. Example 36 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 6 and the results therefrom are set forth in Table XI. Example 37 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 7 and the results therefrom are set forth in Table XII. Example 38 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 8 and the results therefrom are set forth in Table XIII. Example- 39 In Vitro Growth Hormone Release-Study The procedure set forth in Example 31 was employed in an in vitro growth release study of the peptide of Example 9 and the results therefrom are set forth in Table XIV. Example 40 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 10 and the results therefrom are set forth in Table XV. Example 41 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of thepeptide of Example 11 and the results therefrom are set forth in Table XVI. Examle 42 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 12 and the results therefrom are set forth in Table XVII. Example 43 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 ws employed in an in-vitro growth hormone release study of the peptide of Exmaple 13 and the results therefrom are set forth in Table XVIII. Example 44 In-Vitro Growth -Release-Study The procedure set forth in Example 31 was employed in an in-vitro growth hormone release study of the peptide of Example 14 and the results therefrom are set forth in Table XIX. Example 45 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Examples 15 and the results therefrom are set forth in Table XX. Example 46 In vitro Growth Hormone-Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 16 and the results therefrom are set forth in Table XXI. Example 47 In Vitro Growth Hormone -Release Study The procedure set forth in Example 31 was employed in an in-vitro growth hormone release study of the peptide of Example 17 and the results therefrom are set forth in Table XXII. Example 4-8 In Vitro Growth -Hormone-Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Exmaple 18 and the results therefrom are set forth in Table XXIII. Example 49 In V-itro Growth Hormone -Release Study The procedure set forth in Example 31 was employed in an in-vitro growth hormone release study of the peptide of Example 19 and the results therefrom are set forth in Table XXIV. Example 50 In Vitro Growth Hormon-eRelease Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 20 and the results therefrom are set forth in Table XXV. Example 51 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 21 and the results therefrom are set forth in Table XXVI. Example 52 In-Vitro Growth Hormone Releas-e Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Exmaple 22 and the results therefrom are set forth in Table XXVII. Example 53 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in-vitro growth hormone release study of the peptide of Exmaple 23 and the results therefrom are set forth in Table XXVIII. Example 54 In- Vitro Growth -Hormone Release Study The procedure set forth in Example 31 was employed in an in-vitro growth hormone release study of the peptide of Example 24 and the results therefrom are set forth in Table XXIX. Example- - 55 In- -Vitro -Growth- Hormon-e Release Study The procedure set.forth in Example 31 was employed in an vitro growth hormone release study of the peptide of Example 25 and the results therefrom are set forth in Table XXX. Example 56 In Vitro Growth Hormone Rele-ase Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 26 and the results therefrom are set forth in Table XXXI. Example 57 In Vitro Growth Hormone Release St-udy The procedure set forth in Example 31 was employed in an in-vitro growth hormone release study of the peptide of Example 27 and the results therefrom are set forth in Table XXXII. Example 58 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in-vitrs growth hormone rlease study of thepeptide of Example 28 and the results therefrom are set forth in Table XXXIII. Example 59 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 29 and the results therefrom are set forth in Table XXXIV. Example- 60 In Vitro Growth-Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 30 and the results therefrom are set forth in Table XXXV. TABLE VI IN VITRO GROWH HORMONE RELEASE Dosageê AGHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-NH2 - -167#114 1 206#168 NS 3 288# 79 < 0.01 10 2,005#203 < 0.001 30 3,046# 93 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3.NS denotes not significant 4. Comparation of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE VII IN VITRO GROWTH HORMONE RELEASE Dosageê AGHÚ p Value4 H2-Tyr-D-Trp-Ala-Trp-D-His-NH2 - -167#114 1 -179#323 NS 3 -192#120 NS 10 -802#302 NS 30 611#103 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growht hormone agonist analog to the GH levels in medium without the agonist TABLE VIII IN VITRO GROWTH HORMONE RELEASE Dosageê AGHÚ p Value4 H2-Tyr-D-Trp-Ala-Trp-D-Tyr-NH2 - -236#125 1 -126#253 NS 10 - 99#230 NS 100 -238#133 NS 1,000 2,598#284 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growht hormone agonist analog to the GH levels in medium without the agonist TABLE IX IN VITRO GROWTH HORMONE RELEASE Dosageê AGHÚ p Value4 H2-Tyr-D-Trp-Ala-Trp-D-His-NH2 - -236#125 1 -166#277 NS 10 -369#152 NS 100 43#185 NS 1,000 1,501#222 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growht hormone agonist analog to the GH levels in medium without the agonist TABLE X IN VITRO GROWTH HORMONE RELEASE Dosageê AGHÚ p Value4 H2-Tyr-D-Trp-Ala-Trp-D-p-Cl-Phe-NH2 - 28#54 1 -87#81 NS 30 124#123 NS 300 103#77 NS 3,000 531# 42 < 0.001 30,000 489#138 < 0.01 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growht hormone agonist analog to the GH levels in medium without the agonist TABLE XI IN VITRO GROWTH HORMONE RELEASE Dosageê AGHÚ p Value4 H2-Tyr-D-Trp-Ala-Trp-D-Phe-NH2 - -257# 97 300 648#210 < 0.02 3,000 435#143 < 0.02 30,000 1,136#190 < 0.001 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growht hormone agonist analog to the GH levels in medium without the agonist TABLE XII IN VITRO GROWTH HORMONE RELEASE Dosageê AGHÚ p Value4 H2-p-Cl-Phe-D-Ala-Trp-D-Phe-NH2 - -218#161 30 -260#271 NS 300 367#159 < 0.05 1,000 714#110 < 0.01 10,000 1,326#143 < 0.001 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growht hormone agonist analog to the GH levels in medium without the agonist TABLE XIII IN VITRO GROWTH HORMONE RELEASE Dosageê AGHÚ p Value4 H2-desaminoTyr-D-Trp-Ala-Trp-D-Phe-NH2 - 28# 54 30 231# 65 < 0.02 300 432#109 < 0.01 3,000 700#201 < 0.01 20,000 -861# 13 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growht hormone agonist analog to the GH levels in medium without the agonist TABLE XIV IN VITRO GROWTH HORMONE RELEASE Dosageê AGHÚ p Value4 CH3CO-Tyr-D-Trp-Ala-Trp-D-Phe-NH2 - -175# 58 10 -297# 79 NS 30 -118# 97 NS 300 5# 29 < 0.02 3,000 1,594#385 < 0.001 30,000 1,607#250 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growht hormone agonist analog to the GH levels in medium without the agonist TABLE XV IN VITRO GROWTH HORMONE RELEASE Dosageê AGHÚ p Value4 H2-O-Me-Tyr-Ala-Trp-D-Phe-NH2 - -9#66 300 177#166 NS 3,000 1,138#266 < 0.001 30,000 892#388 < 0.05 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growht hormone agonist analog to the GH levels in medium without the agonist TABLE XVI IN VITRO GROWTH HORMONE RELEASE Dosageê AGHÚ p Value4 H2-Tyr-D-Trp-Ala-Trp-D-Phe-Met-NH2 - -148#137 30 456#151 NS 300 1,260#245 < 0.01 1,000 1,832#441 < 0.01 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growht hormone agonist analog to the GH levels in medium without the agonist TABLE XVII IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-Thr-NH2 - -40 # 35 10 94 # 69 NS 100 650 # 320 NS 1,000 2,167 # 591 < 0.01 10,000 2,957 # 834 < 0.01 1. The mean of 6 assays given in terms of ng/ml incubation # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XVIII IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-Tyr-D-Trp-Ala-Trp-D-Phe-Gln-OH - -40 # 35 100 753 # 559 NS 1,000 2,759 # 515 < 0.001 10,000 3,994 # 1,214 < 0.01 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Coparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XIX IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-Tyr-D-Trp-Ala-Trp-D-Phe-Gln-NH2 - -40 # 35 10 240 # 96 NS 100 2,000 # 523 < 0.01 1,000 4,235 # 576 < 0.001 10,000 4,141 # 576 < 0.001 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XX IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-Tyr-D-Trp-Ala-Trp-D-Phe-Asn-NH2 - -89 # 51 30 244 # 58 < 0.01 100 528 # 184 < 0.01 1,000 1,670 # 126 < 0.001 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXI IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 - -167 # 114 1 955 # 272 < 0.01 3 1,603 # 305 < 0.001 10 2,244 # 173 < 0.001 30 2,198 # 358 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXII IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-Tyr-D-Trp-Ala-Trp-D-Phe-Lys-NH2 - -29 # 59 30 1,346 # 328 < 0.001 300 2,160 # 166 < 0.001 3,000 1,630 # 135 < 0.001 30,000 1,318 # 247 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXIII IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-Tyr-D-Trp-Ala-Trp-D-Phe-Glu-NH2 - -29 # 59 30 224 # 98 < 0.01 300 472 # 104 < 0.01 3,000 1,404 # 179 < 0.001 30,000 1,909 # 270 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXIV IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-Tyr-D-Trp-Ala-Trp-D-Phe-Phe-NH2 - 29 # 164 30 10 # 57 NS 300 330 # 43 NS 3,000 710 # 67 #0.001 30,000 1,484 # 135 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXV IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-Tyr-D-Trp-Ala-Trp-D-Phe-Gln-NH2 - -89 # 50 30 103 # 248 NS 100 167 # 65 < 0.02 1,000 1,092 # 42 < 0.001 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXVI IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-His-D-Trp-Ala-Trp-D-Phe-Lys-OH - -146 # 67 1 467 # 178 < 0.01 10 330 # 167 < 0.02 100 2,441 # 353 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXVII IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-His-D-Trp-Ala-Trp-D-Phe-Arg-NH2 - -88 # 56 1 805 # 152 < 0.001 3 997 # 249 < 0.001 10 2,064 # 34 6 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XVIII IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-Gln-NH2 - -288 # 182 1 5 # 136 NS 3 140 # 168 NS 10 275 # 66 #0.02 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXIX IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-Glu-NH2 - -251 # 105 1 -78 # 72 NS 3 -294 # 75 NS 10 -243 # 71 NS 30 117 # 41 < 0.01 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXX IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-His-D-Trp-Ala-Trp-D-Phe-HomoArg-NH2 - -553 # 105 1 -150 # 124 < 0.01 10 1,096 # 341 < 0.01 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXXI IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-3-N-Me-D-Trp-Ala-Trp-D-Phe-Lys-NH2 - 435 # 176 1 165 # 136 NS 10 1,857 # 254 < 0.01 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXXII IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-Lis-NHCH2CH3 - 435 # 176 1 726 # 115 NS 10 1,688 # 300 < 0.01 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXXIII IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-Orn-NH2 - -553 # 105 1 -295 # 58 NS 10 356 # 92 < 0.001 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXXIV IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-His-D-Trp-Val-Trp-D-Phe-Lys-NH2 - -553 # 105 30 -118 # 65 < 0.01 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist TABLE XXXV IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ser-Trp-D-Phe-Lys-NH2 - -125 # 132 10 161 # 157 NS 30 705 # 149 < 0.01 1. The mean of 6 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist The results set forth in Tables VI-XXXV demonstrate that peptides within the scope of the instant invention can induce a significant in vitro release of growth hormone from the pituitary. By introducing various other hormones, e.g., somatostatin, testosterone, cortisol, insulin, etc., into the incubation medium of Examples 11-30, one can study what effect these latter hormones have on the regulation of growth hormone secretion. Example 61 In Vivo Growth Hormone Release Study Female rats of the CD-1 strain were housed in a constant temperature room at 24"C. with 14 hours light and 10 hours darkness. The rats were fed Purina brand rat chow ab libitum. All studies were started between 0800 and 1000 hours. Each female rat (21 days old; eight rats per dosage level shown in Table XVI) was intraperitoneally injected with a desired dosage of the peptide of Example 1. Approximately 15 minutes after injection, the rat was guillotined. A blood sample was collected from the guillotined rat. The blood sample was centrifuged and a serum sample was collected therefrom. Each serum sample was assayed for GH, in duplicate, by a standard radioimmunoassay (RIA). The mean of the GH values obtained per dosage level are set forth in Table XXXVI. Example 62 In Vivo Growth Hormone Release Study The procedure set forth in Example 61 was employed in an in vivo growth hormone release study of the peptide of Example 21 and the results therefrom are set forth in Table XXXVII. Example--6-3 In-Vivo -Growth- Hormone -Release-Study The procedure set forth in Example 61 was employed in an in viva growth hormone release study of the peptide of Example 22 and the results therefrom are set forth in Table XXXVIII. Example 64 In Vivo Growth Hormone Release Study The procedure set forth in Example 61 was employed in an in vivo growth hormone release study of the peptide of Example 23 and the results therefrom are set forth in-Table XXXIX. Example 65 In Vivo Growth Hormone Release Study The procedure set forth in Example 61 was employed in an in vivo growth hormone release study of the peptide of Example 24 and the results therefrom are set forth in Table XXXX. Example 66 In Vivo Growth Hormone Release-Study The procedure set forth in Example 61 was employed in an in vivo growth hormone release study of the peptide of Example 25 and the results therefrom are st forth in Table XXXXI. Example 67 In Vivo Growth Hormone Release Study The procedure set forth in Example 61 was employed in an in vivo growth hormone release study of the peptide of Example 26 and the results therefrom are set forth in Table XXXXII. Example 68 In Vivo-Growth -Hormone Release Study The procedure set forth in Example 61 was employed in an in-vivo growth hormone release study of the peptide of Example 27 and the results therefrom are set forth in Table XXXXIII. Example 69 In Vivo Growth Hormone Release Study The procedure set forth in Example 61 was employed in an in vivo growth hormone release study of the peptide of Example 16 and the results therefrom are set forth in Table XXXXIV. TABLE XXXVI IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-NH2 Control 4 # 1 0.1 1 # 1 < 0.05 1.0 2 # 2 NS 10.0 2 # 1 NS 100.0 82 # 18 < 0.001 1. The mean of 8 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM)' 2. Given in terms of g/ml serum 3. NS denotes not significant 4. GH levels in serum of rats intraperitonally injected with peptide compared to the GH levels in serum of control rats TABLE XXXVII IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-His-D-Trp-Ala-Trp-D-Phe-Lys-OH Control 1.7 # 1 30 76 # 24 < 0.01 100 119 # 25 < 0.001 1,000 226 # 43 < 0.001 1. The mean of 8 assays given in terms of ng/ml subcutaneous medium # standard error of the mean (SEM) 2. Given in terms of g/ml serum 3. GH levels in serum of rats subcutaneously injected with peptide compared to the GH levels in serun of control rats TABLE XXXVIII IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-Arg-NH2 Control 5.7 # 2.2 1.0 9.2 # 3.4 NS 3.0 32.2 # 5.5 < 0.001 10.0 87.5 # 31 0.02 30.0 31.1 # 3.4 < 0.001 1. The mean of 8 assays given in terms of ng/ml subcutaneous # standard error of the mean (SEM) 2. Given in terms of g/ml incubation medium 3. NS denotes not significant 4. GH levels in serum of rats subcutaneously injected with peptide compared to the GH levels in serum of control rats TABLE XXXIX IN VIVO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-Gln-NH2 Control 4.9 # 0.9 1.0 1.4 # 0.9 NS 3.0 3.8 # 2.1 NS 10.0 32.1 # 11.4 < 0.05 1. The mean of 9 assays given in terms of ng/ml subcutaneous # standard error of the mean (SEM) 2. Given in terms of g/ml serum 3. NS denotes not significant 4. GH levels in serum of rats subcutaneously injected with peptide compared to the GH levels in serum of control rats TABLE XXXX IN VIVO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-Glu-NH2 Control 0.34 # 0.19 1.0 0.10 # 0 NS 3.0 1.50 # 0.56 NS 10.0 1.4 # 0.78 NS 30.0 8.06 # 2.68 #0.01 1. The assays given in terms of ng/ml subcutaneous # standard error of the mean (SEM) 2. Given in terms of g/ml serum 3. NS denotes not significant 4. GH levels in serum of rats subcutaneously injected with peptide compared to the GH levels in serum of control rats TABLE XXXXI IN VIVO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-HomoArg-NH2 Control 0 # 0 0.3 3 # 2 NS 10.0 62 # 8 < 0.001 1. The mean of 6 assays given in terms of ng/ml subcutaneous # standard error of the mean (SEM) 2. Given in terms of g/ml serum 3. NS denotes not significant 4. GH levels in serum of rats subcutaneously injected with peptide compared to the GH levels in serum of control rats TABLE XXXXII IN VIVO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-3-N-Me-His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 Control 1.1 # 0.6 0.3 45.0 # 10 #0.001 10.0 128 # 16 < 0.001 1. The mean of 6 assays given in terms of ng/ml subcutaneous # standard error of the mean (SEM) 2. Given in terms of g/ml serum 3. GH levels in serum of rats subcutaneously injected with peptide compared to the GH levels in serum of control rats TABLE XXXXIII IN VIVO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value H2-His-D-Trp-Ala-Trp-D-Phe-Lys-NHCH2CH3 Control 1.1 # 0.6 0.3 13.0 # 5 < 0.05 10.0 119 # 12 < 0.001 1. The mean of 6 assays given in terms of ng/ml subcutaneous # standard error of the mean (SEM) 2. Given in terms of g/ml serum 3. GH levels in serum of rats subcutaneously injected with peptide compared to the GH levels in serum of control rats TABLE XXXXIV IN VIVO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value4 H2-His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 Control 0 # 0 0.3 6 # 4 NS 1.0 36 # 15 < 0.04 3.0 66 # 15 #0.001 10.0 100 # 19 < 0.001 30.0 122 # 4 < 0.001 1. The mean of 6 assays given in terms of ng/ml subcutaneous # standard error of the mean (SEM) 2. Given in terms of g/ml serum 3. NS denotes not significant 4. GH levels in serum of rats subcutaneously injected with peptide compared to the GH levels in serum of control rats The results set forth in Tables XXVI-XXXXIV demonstrate that some peptides within the scope of this invention can induce a significant in vivo release of growth hormone. Example 7-0 In Vitra-Growt-h Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the growth promoting agent zeranol, C18H2605, and the results therefrom are set forth in Table XXXXV. Example 71 In Vitro Growth Hormone Release Study The procedure set forth in Example 31 was employed in an in vitro growth hormone release study of the peptide of Example 21 in combination with the growth promoting agent zeranol, C18H2605, and the results therefrom are set forth in Table XXXXVI. The results set forth in Table XXXXVI, when compared to the results set forth in Tables XXVI and XXXXV, demonstrate that a combination within the scope of the instant invention can induce a synergistic in vitro release of growth hormone from the pituitary. TABLE XXXXV IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p Value Zeranol, C18H2605 - -115 # 49 300 83 # 63 0.02 3,000 87 # 59 < 0.02 30,000 683 # 187 < 0.001 100,000 -133 # 98 NS 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of g/ml incubation medium 3. NS denotes not significant 4. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agoinst TABLE XXXXVI IN VITRO GROWTH HORMONE RELEASE DOSAGEê #GHÚ p. Value Zeronol, C18H26O3(A) H2-His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 - -309 # 39 3,000 A + 1B 2,183 # 399 < 0.001 3,000 A + 3B 2,114 # 336 < 0.001 30,000 A + 1B 2,266 # 327 < 0.001 30,000 A + 3B 2,761 # 356 < 0.001 1. The mean of 9 assays given in terms of ng/ml incubation medium # standard error of the mean (SEM) 2. Given in terms of ng/ml incubation medium 3. Comparison of the GH levels in medium containing growth hormone agonist analog to the GH levels in medium without the agonist Based on this disclosure, many other modifications and ramifications will naturally suggest themselves to those skilled in the art. These are intended to be comprehended as within the scope of this invention.

Claims: The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 1. A peptide having a formula selected from a group consisting of EMI119.1 wherein X1, X2(X1 , X2', and X3 are selected from a group consisting of N-terminal and desamino alphacarbon substitutions; a and b are 0 or 1, provided that a and b are 0 when A1 is a desamino residue; A1 and A4 are selected from a group consisting of His, Arg, Lys, a-Naphth, B-Naphth, Iql, Tyr, Trp, Phe, homologues and analogues thereof, and, with respect to A1 the desamino forms thereof; ; A2 and As are selected from a group consisting of D-His, D-Arg, D-Lys, D-a-Naphth, D-B-Naphth, D Iql, D-Tyr, D-Trp, D-Phe, homologues and analogues thereof, and, with respect to A5, the descarboxy forms thereof; A3 is selected from a group consisting of Gly, Ala, Val, Leu, Ile, Pro, Ser, Thr, Met, Asp, Glu, Asn, Gln, His, D-Ala, D-Val, D-Leu, D-Ile, D-Pro, D Ser, D-Thr, D-Met, D-Asp, D-Glu, D-Asn, D-Gln, D His, and homologues and analogues thereof; A6 is selected from a group consisting of amino acids of the L- and D- configuration, homologues and analogues thereof, and the descarboxy forms thereof; and Y is selected from a group consisting of Cterminal and descarboxy alpha-carbon substitutions; and the pharmaceutically acceptable salts thereof; provided that, when (1) a is 1 and b is 0 and X1 and X2 are selected from the group consisting of -H and -CH3; (2) A1 and A4 are selected from the group consisting of Tyr, Trp, and Phe; (3) A3 is selected from the group consisting of Gly, Ala, Val, Leu, Ile, Pro, Ser, Thr, Met, Asp, Glu, Asn, Gln, and His; and (4) Y is selected from the group consisting of -NR1R2, -CH2OR, and -OR, wherein R, Ri, and R2 are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of A2 and A5 is selected such that it is not from the group consisting of D-Tyr, D-Trp, D-Pfle, and, with respect to As, the descarboxy forms thereof; when (1) a is 1 and b is 0 and X1 and X2 are selected from the group consisting of -H and -CH3; (2) A2 and As are selected from the group consisting of D-Tyr, D-Trp, D-Phe, and, with respect to A5, the descarboxy forms thereof; (3) A3 is selected from the group consisting of Gly, Ala, Val, Leu, Ile, Pro, Ser, Thr, Met, Asp, Glu, Asn, Gln, and His; and 14) Y is selected from the group consisting of -NR1R2, -CH2OR, and -OR, wherein R, R1, R2 are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of A1 and A4 is selected such that is is not from a group consisting of Tyr, Trp, and Phe; (1) when a is 1 and b is 0 and X1' and X2' are selected from the group consisting of -H, -CH3, anci -CHOCH3; (2) Al and A4 are selected from the group consisting of Tyr, Trp, and Phe; (3) A3 is selected from the group consisting of Gly, Ala, Val, Leu, Ile, Ser, Thr, Met, Asn, and Gln; (4) A6 is selected from the group consisting of Asn, Gln, Glu, Arg, Lys, Ser, Thr, and the descarboxy forms thereof; and (5) Y is selected from the group consisting of -NRlR2, -CH2OR, and -OR, wherein R, R1, and R2 are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of A2 and As is selected such that it is not from the group consisting of D-Tyr, D-Trp, and D-Phe; and when (1) a is 1 and b is 0 and X1' and X2 are selected from the group consisting of -H, -CH3 and PCHOCH3; (2) A2 and A5 are selected from the group consisting of D-Tyr, D-Trp, and D-Phe; (3) A3 is selected from the group consisting of Gly, Ala, Val, Leu, Ile, Ser, Thr, Met, Asn, and Gln; (4) A6 is selected from the group consisting of Asn, Gln, Glu, Arg, Lys, Ser, Thr, and the descarboxy forms there of; and (5) Y is selected from the group consisting of -NR1R2, -CH2OR, and -ORj wherein R, R1, R2 are selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of A1 and A4 is selected such that it is not from a group consisting of Tyr, Trp, and Phe. 2. The peptide of claim 1 wherein: a is 0 or 1 and b is 0; Xl, X2, X1' and X2' are selected from a group consisting of -R, -OR, and RC(O)-, wherein R is selected from a group consisting of hydrogen and straight and branched chain alkyl group containing 1-6 carbon atoms; A1 and A4 are selected from the group consist ing of His, Tyr, Trp, Phe, homologues and analogues thereof, and, with respect to A1, the desamino forms thereof; A2 and As are selected from the group consist ing of D-His, D-Tyr, D-Trp, D-Phe, homologues and analogues thereof, and, with respect to A5, the descarboxy forms thereof; A3 is selected from the group consisting of Gly, Ala, Ser, Asn, Pro, D-Ala, D-Ser, D-Asn, D-Pro, and homologues and analogues thereof; ; A6 is selected from the group consisting of Arg, Lys, Orn, His, Asp, Glu, Asn, Gln, D-Arg, D Lys, D-Orn, D-His, D-Asp, D-Glu, D-Asn, D-Gln, D Arg, homologues and analogues thereof, and descar boxy forms thereof; Y is selected from the group consisting of -CH2OH, -OR, and -NR1R2, wherein R, R1 and R2 are selected from the group consisting of hydrogen and straight or branched chain alkyl group containing 1 6 carbon atoms; and the pharmaceutically acceptable salts thereof. 3. The peptide of claim 1 having the formula selected from the group consisting of EMI122.1 wherein a is 0 or 1; X2 and X21 are selected from the group consist ing of RCO and R- wherein R is selected from the group consisting of hydrogen and alkyl groups con taining 1-2 carbon atoms; A1 is selected from the group consisting of Tyr, O-Me-Tyr, His, 3-N-Me-His, p-Cl-Phe, and the desamino forms thereof; A3 is selected from the group consisting of Ala, Ser, and D-Ala; A4 is selected from the group consisting of Trp and Tyr; As is selected from the group consisting of D Phe, D-His, D-Tyr, and D-p-Cl-she; A6 is selected from the group consisting of Arg, HomoArg, Lys, Orn, Asp, Glu, Asn, Gln, and D Lys; ; Y is selected from the group consisting of -OR, and -NHR, wherein R is selected from the group con sisting of hydrogen and alkyl groups containing 1-2 carbon atoms; and the pharmaceutically acceptable salts thereof. 4. The peptide of claim 1 of the formula selected from a group consisting of -H2-His-D-Trp-Ala-Trp-D-phe-NH2, H2-Tyr-D-Trp-Ala-Trp-D-His-NH2 H2-His-D-Trp-Ala-Trp-D-His-NH2, H2-His-D-Trp-Ala-Trp-D-Tyr-NH2i H2-Tyr-D-Trp-Ala-Trp-D-p-Cl-Phe-NH2, H2-p-Cl-Phe-D-Trp-Ala-Trp-D-Phe-NH2, H-desaminoTyr-D-Trp-Ala-Trp-D-Phe-NH2, EMI123.1 H2-O-Me-Tyr-D-Trp-Ala-Trp-D-Phe-NH2r H2-Tyr-D-Trp-Ala-Trp-D-Phe-Met-NH2, H2-Tyr-D-Trp-Ala-Trp-D-Phe-Thr-NH2, H2-Tyr-D-Trp-Ala-Trp-D-Phe-Gln-OH, H2-Tyr-D-Trp-Ala-Trp-D-Phe-Gln-NH2r H2-Tyr-D-Trp-Ala-Trp-D-Phe-Asn-NH2, H2-Hi s-D-Trp-Ala-Trp-D-Phe-Lys-NH2, H2-Tyr-D-Trp-Ala-Trp-D-Phe-Lys-NH2, H2-Tyr-D-Trp-Ala-Trp-D-Phe-Glu-NH H2-Tyr-D-Trp-Ala-Trp-D-Phe-Phe-NH2, H2-Tyr-D-Trp-Ala-Trp-D-Phe-Gln-NH2, H2-His-D-Trp-Ala-Trp-D-Phe-Lys-OH, H2-His-D-Trp-Ala-Trp-D-Phe-Arg-NH2r H2-His-D-Trp-Ala-Trp-D-Phe-Gln-NHz, H2-His-D-Trp-Ala-Trp-D-Phe-Glu-NH2r H2-His-D-Trp-Ala-Trp-D-Phe-HomoArg-NH2, H2-3-N-Me-His-D-Trp-Ala-Trp-D-Phe-Lys-NH H2-His-D-Trp-Ala-Trp-D-Phe-Lys-NHCH2CH3, H2-His-D-Trp-Ala-Trp-D-Phe-Orn-NH2, H2-His-D-Trp-Val-Trp-D-Phe-Lys-NH2, and H2-His-D-Trp-Ser-Trp-D-Phe-Lys-NH2. 5. A combination comprising: (a) at least one growth promoting agent; and (b) at least one peptide of any one of claims 1-3 or 4. 6. The combination of claim 5 wherein said peptide has the formula H2-His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 and wherein said growth promoting agent is zeronol, C18H260. 7. A method of releasing growth hormone from a pitui tary comprising contacting said pituitary with the peptide of any one of claims 1-5 or 6. 8. A method of releasing growth hormone in vivo from a pituitary comprising contacting said pituitary with the peptide of claim 4 having a formula selected from the group consisting of H2-His-D-Trp-Ala-Trp-D-Phe-NH2, H2-His-D-Trp-Ala-Trp-D-Phe-Lys-NH2r H2-His-D-Trp-Ala-Trp-D-Phe-Lys-OH, H2-His-D-Trp-Ala-Trp-D-Phe-Arg-NH2, H2-His-D-Trp-Ala-Trp-D-Phe-Gln-NH2, H2-His-D-Trp-Ala-Trp-D-Phe-Glu-NH2r H2-His-D-Trp-Ala-Trp-D-Phe-HomoArg-NH2, H2-3-N-Me-His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, and H2-His-D-Trp-Ala-Trp-D-Phe-Lys-NHCH2CH3. 9. An intermediate composition having a formula se lected from a group consisting of EMI125.1 EMI126.1 B1-B2-B3-B4-B' 5-Y(X) EMI126.2 BI-B2-B3-B4-BS-B' 6-Y(XIII) wherein Prl is an a-amino acid protecting group; a, b, m, q, r, and s are each 0 or 1; X'''1, X'''2, X'''3, Xiv2 and Xiv3 are selected from a group consisting of N-terminus and desamino alpha-carbon substitutions and radicals; B1 and B4 are selected from a group consisting of His, Arg, Lys, a-Naphth, B-Naphth, Iql, Tyr, Trp, Phe, homologues and analogues thereof, the side chain protected forms thereof, and, with respect to B1' the desamino forms thereof; ; B2, B5, and B'5 are selected from a group consisting of D-His, D-Arg, D-Lys, D-a-Naphth, D-ss- Naphth, D-Iql, D-Tyr, D-Trp, D-Phe, homologues and analogues thereof, the side-chain protected forms thereof, and, with respect to B'5, the descarboxy forms thereof; B3 is selected from a group consisting of Gly, Ala, Val, Leu, Ile, Pro, Ser, Thr, Met, Asp, Glu, Asn, Gln, His, D-Ala, D-Val, D-Leu, D-Ile, D-Pro, D Ser, D-Thr, D-Met, D-Asp, D-Glu, D-Asn, D-Gln, D Arg, D-His, homologues and analogues thereof, and the side-chain protected forms thereof; B6 and B'6 are selected from a group consisting of amino acids of the L- and D- configurations, homologues and analogues thereof, the side chain protected forms thereof, and, with respect to B'6' the descarboxy forms thereof; &commat; ; is a resin; Y is selected from a group consisting of Cterminal and descarboxy alpha-carbon substitutions; and Pr2 is a carboxyl protecting group; provided that, when (1) a is 1 and b and m are 0 and X"'2 is selected from the group consisting of -H and -CH3; (2) B1 and B4 are selected from the group consisting of Tyr, Trp, Phe, and the sidechain protected forms thereof; (3) B3 is selected from the group consisting of Gly, Ala, Val, Leu, Ile, Pro, Ser, Thr, Met, Asp, Glu, Asn, Gln, His, and the side-chain protected forms thereof; and, with respect to IV and VI, (4) Y is selected from the group consisting of -NH1R2, -OR, and -CH2OR, wherein each R, R1, and R2 is selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of B2, B5, or B'5 is selected such that it is not from a group consisting of D-Tyr, D-Trp, D-Phe, and, with respect to B's, the descarboxy forms thereof, and the side-chain protected forms thereof; when (1) a is 1 and b and m are 0 and X'''2 is selected from the group consisting of -H and -CH3; (2) B2 and B5 or B's are selected from the group consisting of D-Tyr, D-Trp, D-Phe, and, with respect to B'5, the descarboxy forms thereof, and the sidechain protected forms thereof; (3) B3 is selected from the group consisting of Gly, Ala, Val, Leu, Ile, Pro, Ser, Thr, Met, Asp, Glu, Asn, Gln, His and the side-chain protected forms thereof; and, with respect to IV and VI, (4) Y is selected from the group consisting of -NR1R2, -OR, and -CH2OR, wherein each R, R1, and R2 is selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of B1 and B4 is selected such that it is not from a group consisting of Tyr, Trp, Phe, and the side-chain protected forms thereof; when (1) a is 1 and b and m are 0 and Xiv2 is selected from the group consisting of -H, -CH3, and -CHOCH3; (2) B1 and B4 are selected from the group consisting of Tyr, Trp, Phe, and the side-chain protected forms thereof; (3) B3 is selected from the group consisting of Gly, Ala, Val, Leu, Ile, Ser, Thr, Met, Asn, Gln, and the side-chain protected forms thereof; (4) B6 or B'6 is selected from the group consisting of Asn, Gln, Glu, Arg, Lys, Ser, Thr, and, with respect to B'6, the descarboxy forms thereof, and the side-chain protected forms thereof; and, with respect to XI and XIII, (5) Y is selected from the group consisting of -NH1R2 -OR, and -CH2OR, wherein each R, R1, and R2 is selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of B2 or B5 is selected such that it is not from a group consisting of D Tyr, D-Trp, D-Phe, and the side-chain protected forms thereof; and when (1) a is 1 and b and m are 0 and Xiv2 is selected from the group cnsisting of -H, -CH3, and CHOCH3; (2) B2 and B5 are selected from the group consisting of D-Tyr, D-Trp, D-Phe, and the sidechain protected forms thereof; (3) B3 is selected from the group consisting of Gly, Ala, Val, Leu, Ile, Ser, Thr, Met, Asn, Gln, and the side-chain protected forms thereof; (4) B6 or B6 is selected from the group consisting of Asn, Gln, Glu, Arg, Lys, Ser, Thr, and, with respect to B'6r the descarboxy forms thereof, and the side-chain protected forms thereof; and, with respect to XI and XIII, (5) Y is selected from the group consisting of PNR1R2, -OR, and -CH2OR, wherein each R, R1, and R2 is selected from a group consisting of hydrogen and straight and branched chain alkyl groups containing 1-6 carbon atoms; then at least one of B1 and B4 is selected such that it is not from a group consisting of Tyr, Trp, Phe, and the side-chain protected forms thereof. 10. The intermediate composition of claim 9 wherein: B1 and B4 are selected from the group consist ing of His, Tyr, Trp, Phe, homologues and analogues thereof, and, with respect to B1, the desamino forms thereof, and the side-chain protected forms thereof; B2, Bg, and B'5 are selected from the group consisting of D-His, D-Tyr, D-Trp, D-Phe, homologues and analogues thereof, and, with respect to B'5, the descarboxy forms thereof, and the side-chain pro tected forms thereof; B3 is selected from the group consisting of Gly, Ala, Ser, Asn, Pro, D-Ala, D-Ser, D-Asn, D-Pro, homologues and analogues thereof, and the side-chain protected forms thereof; and B6 and B'6 are selected from the group consist ing of Arg, Lys, Orn, His, Asp, Glu, Asn, Gln, D Arg, D-Lys, D-Orn,D-His, D-Asp, D-Glu, D-Asn, D-Gln, homologues and analogues thereof, and, with respect to B'6, the descarboxy forms thereof, and the side chain protected forms thereof. 11. The intermediate composition of claim 9 having the formula selected from the group consisting of EMI130.1 EMI131.1 B1-D-Trp-B3-B4-B'5-Y(XVIII) EMI131.2 B1-D-Trp-B3-B4-B5-B'6-Y(XXI) wherein B1 is selected from the group consisting of Tyr, O-Me-Tyr, His, 3-N-Me-His, p-Cl-Phe, the des amino forms thereof, and the side-chain protected forms thereof; B3 is selected from the group consisting of Ala, Ser, D-Ala, and the side-chain protected forms thereof; B4 is selected from the group consisting of Trp, Tyr, and the side-chain protected forms there of; and B5 and Bts are selected from the group consist ing of D-Phe, D-His, D-Tyr, D-p-Cl-Phe, and, with respect to B'5, the descarboxy forms thereof, and the side-chain protected forms thereof; and B6 and B'6 are selected from the group consist ing of Arg, HomoArg, Lys, Orn, Asp, Glu, Asn, Gln, D-Lys, the descarboxy forms thereof, and the side chain protected forms thereof. 12. The intermediate composition of claim 9 of the for mula selected from the group consisting of Boc-His(Tos)-D-Trp-Ala-Trp-D-Phe-&commat;, Boc-Tyr(BrZ)-D-Trp-Ala-Trp-D-His(Tos)-#, Boc-His(Tos)-D¯Trp-Ala-Trp-D-His(Tos)-#, Boc-His(Tos)-D-Trp-Ala-Trp-D-Tyr(BrZ)-&commat;, Boc-Tyr ( BrZ) -D-Trp-Ala-Trp-D-p-Cl-Phe-&commat;, Boc-Tyr(BrZ)-D-Trp-Ala-Trp-D-Phe-&commat;, Boc-p-Cl-Phe-D-Trp-Ala-Trp-D-Phe-#, 3(p-OH-phenyl)propanoic acid-D-Trp-Ala Trp-D-p-Cl-Phe-#, Boc-O-Me-Tyr(BrZ)-D-Trp-Ala-Trp-D-Phe-#, Boc-Tyr(brZ)-D-Trp-Ala-Trp-D-Phe-Met-#, Boc0Tyr(Brz)-D-Trp-Ala-Trp-D-Phe-Thr(Bzl) #, Boc-Tyr(BrZ)-D-Trp-Ala-Trp-D-Phe-Glu-&alpha;- benzyl ester-&commat; ; Boc-Tyr(BrZ)-D-Trp-Ala-Trp-D-Phe-Gln-e, Boc-Tyr(BrZ)-D-Trp-Ala-Trp-D-Phe-Asn-#, Boc-His(Tos)-D-Trp-Ala-Trp-D-Phe-Lys(ClZ) #, Boc-Tyr(BrZ)-D-Trp-Ala-Trp-D-His(Tos) Lys(ClZ)-&commat;, Boc-Tyr(BrZ)-D-Trp-Ala-Trp-D-Phe-Glu-&gamma; Bzl-&commat;, Boc-Tyr(Brz)-D-Trp-Ala-Trp-D-Phe-Phe-#, Boc-Tyr(BrZ)-D-Trp-Gly-Trp-D-Phe-Gln-ONP #, Boc-His(Tos)-D-Trp-Ala-Trp-D-Phe-Lys(ClZ) #', Boc-His(Tos)-D-Trp-Ala-Trp-D-Phe-Arg(Tos) #, Boc-His(Tos)-D-Trp-Ala-Trp-D-Phe-Gln-ONP #, Boc-His(Tos)-D-trp-Ala-Trp-D-Phe-Glu-&gamma; Bzl-&commat;, Boc-His(Tos)-D-Trp-Ala-Trp-D-Phe HomoArg(Tos)-&commat; ;, Boc-3-N-Me-His-D-Trp-Ala-Trp-D-Phe Lys(ClZ)-e, Boc-His(Tos)-D-Trp-Ala-Trp-D-Phe-Lys(ClZ) #, Boc-His(Tos)-D-Trp-Ala-Trp-D-Phe-Ozn(Z)-#, Boc-His(Tos)-D-Trp-Val-Trp-D-Phe-Lys(ClZ) &commat;, and Boc-His(Tos)-D-Trp-Ser(Bzl)-Trp-D-Phe Lys(ClZ)&commat;, wherein Boc is t-butyloycarbonyl; BrZ is o-bromobrnzyloxycarbonyl; .BrZ. is p-bromobenzyloxycarbonyl; Bzl is benzyl; y-Bzl is y-benzyl ester; ClZ is o-chloro-benzyloxycarbonyl; ONP is -nitrophenyl ester; Tos is p-toluenesulfonyl; Z is benzyloxycarbonyl; &commat; is p-methylbenzhydryalmine resin; and #, is hydroxymethyl resin.

Inventors: BOWERS, CYRIL Y., MOMANY, FRANK A.
Applicants: BECKMAN INSTRUMENTS, INC.
Application year: 1982
Main classification: C07K7
IPC codes: A61K38, A61P43, A61P3, C07K7, C07K14