Peptides with sulfate ester group

Abstract: Novel peptides having sulfate ester groups and containing 6 to 9 amino acids of the formula: possessing feeding inhibition properties and capable of stimulating the contraction of the gallbladder. Also methods of treating and preventing obesity in which these novel peptides or other specified peptides can be used and pharmaceutically acceptable salti thereof.

Description: BACKGROUND OF THE INVENTION This invention concerns sulphate ester containing peptides possessing feeding inhibition properties. These peptides have 6 to 8 amino acids. They all differ structurally, however, from two similarly sized peptides known to have feeding inhibition properties: CCK-8, which has the structure Asp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, and ceruletide, which has the structure Glp-Gln-Asp-Tyr(SO₃H)-Thr-Gly-Trp-Met-Asp-Phe-NH₂. The peptides of this invention are not found in nature but, rather, must be synthesized. SUMMARY OF THE INVENTION The compounds of the invention are peptides of the formula (1) wherein Q is H-βAsp, H-DAsp, For, Ac, Suc, desQ or R¹R²CHOCO; Y is H, (S)-NH or (S)-R³N; M is Met, Ahx, Leu or Ile; X is Met, Ahx, Leu or Ile; J is Asp, DAsp or MeAsp; F¹ is (S)-NH or (S)-R⁴N; R¹ and R² independently represent H or lower alkyl; R³ and R⁴ represent lower alkyl; and pharmaceutically acceptable salts thereof; provided that: (1) Q is desQ when Y is H; (2) Q is not Ac if, in the same peptide: Y is (S)-NH; M is Met, Ahx or Leu; X is Met, Ahx or Leu; J is Asp; and F¹ is (S)-NH; (3) Q is neither H-βAsp nor For if, in the same peptide: Y is (S)-NH; M is Met, Ahx or Leu; X is Met, Ahx or Leu; J is Asp; and F¹ is (S)-NH; (4) Y is not H if, in the same peptide: M is Met; X is Met; J is Asp; and F¹ is (S)-NH; (5) Q is not Suc if, in the same peptide: Y is (S)-NH; M is Met; X is Met; and J is Asp; and (6) Q is not H-DAsp if, in the same peptide: Y is (S)-NH; M is Met; X is Met; J is Asp; and F¹ is (S)-NH. The invention is also a process of making the peptides of the invention. The invention is also methods of treating obesity and preventing obesity, respectively; each such method comprising the administration, by either an intraperitoneal, intravenous, intramuscular, subcutaneous or intranasal route, to a mammal in need of such treatment, of a peptide of the formula (1), without the provisos (2)-(6) and pharmaceutically acceptable salts thereof. DETAILED DESCRIPTION Definitions "lower alkyl" contains 1 to 6 carbon atoms. (S) refers to the absolute configuration about the adjacent methine carbon. When Y is (S)-NH, then is of the L-configuration. Similarly, when F¹ is (S)-NH then is of the L-configuration. All optically active amino acids are of the L-configuration unless otherwise indicated. The H in H-βAsp and H-DAsp stands for hydrogen. DesQ, which arises when Y is H, means that there is no Q. R¹R²CHOCO is the formula Hpp(SO₃H) is the formula Each claim to a compound includes its pharmaceutically acceptable base addition salts. Base addition salts include those derived from both organic and inorganic bases, such as, for example, ammonia, sodium hydroxide, calcium hydroxide, barium hydroxide, tetraethylammonium hydroxide, ethylamine, diethylamine, triethylamine, and the like. In an alternative representation to formula (1), used for purposes of brevity, peptides are also represented in accordance with conventional representation, for example, H-DAsp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, which stands for the compound of formula (1) in which Q is H-DAsp, Y is (S)-NH, X is Met, J is Asp, and F¹ is (S)-NH. When amino acids, peptides, protecting groups, active groups, etc. are represented by symbols in this specification and appended claims, usual symbols as defined by IUPAC and IUB or as used in the art are employed. Examples of symbols are given below. Abu 2-aminobutyric acid Ac acetyl Ahx 2-aminohexanoic acid Aib 2-aminoisobutyric acid Ala alanine Arg arginine Asn asparagine Asp aspartic acid βAsp beta-aspartic acid Boc tert-butyloxycarbonyl BrCH₂-Pam 4-(bromomethyl)phenylacetamidomethyl Cbz carbobenzoxy Cys(Me) S-methylcysteine DAla D-alanine DAhx D,2-aminohexanoic acid DAsp D-aspartic acid DMet D-methionine DPhe D-phenylalanine DPhe-NH₂ D-phenylalanine amide DTrp D-tryptophan DTyr D-tyrosine EtOCO ethyloxycarbonyl EtPhe N-ethylphenylalanine EtPhe-NH₂ N-ethylphenylalanine amide Fmoc 9-fluorenylmethyloxycarbonyl For formyl Gln glutamine Glp pyroglutamyl Glu glutamic acid Glt HOOC(CH₂)₃CO- Gly glycine His histidine Hpp 3-(4-hydroxyphenyl)propionyl Hpp(SO₃H) 3-(O-sulfo-4-oxyphenyl)propionyl iBuOCO isobutyloxycarbonyl Ile isoleucine Leu leucine Lys lysine MeAhx N-methyl-2-aminohexanoic acid MeAsp N-methylaspartic acid MeLeu N-methylleucine MeIle N-methylisoleucine MeMet N-methylmethionine MeOCO methyloxycarbonyl MePhe N-methylphenylalanine MePhe-NH₂ N-methylphenylalanine amide Met methionine MetO methionine sulfoxide MeTrp N-α-methyltryptophan MeTyr N-methyltyrosine MeTyr(Me) N,O-dimethyltyrosine MeTyr(Me)-NH₂ N,O-dimethyltyrosine amide Mox methoxinine Nal 3-(2-naphthyl)alanine OBt 1-benzotriazolyl ester OCH₂-Pam 4-(oxymethylphenyl)acetamidomethyl OSu succinimidyloxy ester OtBu tert-butyl ester Phe phenylalanine Phe-NH₂ phenylalanine amide Phe-NHEt phenylalanine ethylamide Phe-NHMe phenylalanine methylamide Phe-N(Et)₂ phenylalanine diethylamide Phe-N(Me)₂ phenylalanine dimethylamide Phe-OH phenylalanine acid Phe(4-Cl) 3-(4-chlorophenyl)alanine Phe(4-Cl)-NH₂ 3-(4-chlorophenyl)alanine amide Phe(4-Me) 3-(4-methylphenyl)alanine Phe(4-Me)-NH₂ 3-(4-methylphenyl)alanine amide Phe(4-NO₂) 3-(4-nitrophenyl)alanine Phe(4-NO₂)-NH₂ 3-(4-nitrophenyl)alanine amide Phe(4-NH₂) 3-(4-aminophenyl)alanine Phe(4-NH₂)-NH₂ 3-(4-aminophenyl)alanine amide Pht Pro proline PrOCO n-propyloxycarbonyl resin polystyrene Sar sarcosine Ser serine Suc HOOC(CH₂)₂CO- tBu tert-butyl Thr threonine Trp tryptophan Trp(5-F) 5-fluorotryptophan Trp(6-F) 6-fluorotryptophan Trp(Me) 1-methyltryptophan Tyr tyrosine Tyr-NH₂ tyrosine amide Tyr(Me) O-methyltyrosine Tyr(Me)-NH₂ O-methyltyrosine amide Tyr(SO₃H) O-sulfotyrosine Tyr(SO₃H)-NH₂ O-sulfotyrosine amide Val valine Preferred Compounds The preferred compounds from the point of view of feeding inhibition are: The compound, EtOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, inhibited feeding by 72% during the 0.5 hour feeding period when administered at 0.3 µg/kg in the test described under "Utility" below. Preparation of Peptides The novel sulfate ester peptides of this invention and the novel intermediates thereof may be prepared by methods well known to the art, for example, they may be prepared by combining individual amino acids on a solid phase resin on a step-by-step basis, or alternatively, by combining groups of amino acids on a solid phase resin to yield the desired peptidyl-resin intermediate. Such additions, as is known, are accomplished by protecting the amino group of the amino acid or group of amino acids by converting it to, for example, its tert-butyloxycarbonyl (Boc) or 9-fluorenylmethyloxycarbony (Fmoc) derivative, and then activating the carboxylic group of such amino acid or group of amino acids by converting it, for example, to its 1-hydroxyberizotriazole (HOBt) or N-hydroxysuccinimide (HOSu) ester derivative. Such a protected-activated intermediate is then allowed to react with an amino acid-resin or peptidyl-resin with a free amino group, thus extending the peptide chain to provide the peptidyl-resin of formula 2, wherein Pg is a suitable protecting group, for example, Boc or Fmoc. The phenolic OH group within formula (2) is converted to a sulfate ester by the use of a usual sulfating agent, such as sulfur trioxide pyridine complex. More specifically, the reaction is conducted, for example, by suspending a peptidyl-resin of formula 2 in dimethylformamide (DMF), pyridine or like solvent, and adding sulfur trioxide pyridine complex in about 10-40 molar excess to provide the sulfated peptidyl-resin of the formula 3. Since the sulfate ester containing peptide end-products of this invention are C-terminal amides, the chemical link which connects the peptide chain to the resin must be such that its cleavage with suitable reagents readily provides amides. Due to the lability of the sulfate ester group to strong acids (for example, liquid hydrogen fluoride), the peptidyl-resin linkage may be cleavable with either weaker acids (for example, brief treatment with trifluoroacetic acid, TFA) and/or nucleophiles (for example, ammonia, amines, hydroxide, and alkoxides). Among the suitable resin derivatives may be mentioned oxymethyl-polystyrene, 4-(oxymethyl-phenyl)(CH₂) n CO-aminomethyl-polystyrene (n = 0-3) and 4-(oxymethylphenyl)oxymethyl-polystyrene. Similarly substituted polyacrylamide resins are equally well suited as the above polystyrene based resins. For the purposes of this invention the 4-(oxymethylphenyl)CH₂CO-aminomethyl-polystyrene [herein referred to as 4-(oxymethylphenyl)acetamidomethylpolystyrene or OCH₂-Pam-resin] is best suited for the generation of peptide amides. Thus, this invention describes a process for the synthesis of sulfated peptidyl-OCH₂-Pam-resins of formula (4), wherein the resin is polystyrene (the term "polystyrene" includes copolymers with minor amounts, usually 1%, of unsaturated monomers such as divinylbenzene). In forming peptide sequences of this invention, the amino functions may be protected by commonly used amino protecting groups such as Boc, Fmoc, (4-methoxybenzyl)oxycarbonyl, 2-nitrophenylsulfenyl, and so forth. The Boc and Fmoc protecting groups are preferred. The carboxyl and hydroxyl protecting group may be methyl, tert-butyl (tBu), benzyl, 4-methoxybenzyl and so forth. The tBu group is preferred. The amino acid defined by the F¹ group of formula 4 may be attached to the OCH₂-Pam-resin in several ways. (a) For example, Boc protected-phenylalanine, wherein F¹ is (S)-NH may be reacted with a suitable 4-(bromomethyl)-phenylacetate ester (for example, phenacyl ester) and processed further to provide Boc-Phe-(4-oxymethylphenyl)acetic acid which may be coupled to aminomethyl-polystyrene to provide Boc-Phe-(4-oxymethylphenyl)acetamidomethylpolystyrene (Boc-Phe-OCH₂-Pam-resin). (b) Alternatively, 4-(bromomethyl)phenylacetic acid may be coupled to aminomethylpolystyrene to provide 4-(bromomethyl)phenylacetamidomethylpolystyrene (BrCH₂-Pam-resin) which may be reacted with the cesium salt of Boc-Phe-OH to provide Boc-Phe-OCH₂-Pam-resin. Among the suitable activating groups may be mentioned any combination of groups which causes the acid function of the amino acid to become more reactive, such as acid chlorides, mixed and symmetrical anhydrides, reaction product with carbodiimide (for example, dicyclohexylcarbodiimide, DCC), and active esters (for example, esters derived from HOBt, HOSu, 2- or 4-nitrophenol, and 2,4,5-trichlorophenol). The use of DCC and esters of HOBt and HOSu is particularly preferred from the standpoint of yield, lack of by-products, and consequent ease of purification. The protecting groups are removed by known reactions such as treatment with dilute TFA (50% in dichloromethane, DCM) for Boc and/or tBu removal and treatment with dilute piperidine (20% in DMF) for Fmoc removal, to name a few, to provide the sulfated peptidyl-resin of the formula (5). The sulfate ester containing peptides of formula 1 may be obtained by cleavage of the peptidyl-OCH₂-Pam-resin linkage of (5) with the appropriate reagent. The C-terminal sulfated peptide amides are derived, for example, by treatment of the sulfated peptidyl-resin of formula (5) with methanolic solutions of ammonia. An automatic peptide synthesizer was used for the solid phase synthesis of the sulfated peptide amides of this invention. The protocol of coupling onto aminomethyl-resin or peptidyl-OCH₂-Pam-resin (1 mmole of available nitrogen), deprotection, sulfation, cleavage, and product purification is set forth in Table 1. Table 1. Protocol for solid phase synthesis of sulfated peptide amides (1 mmole scale). Each step volume is 50 ml unless otherwise indicated. All wash steps are repeated three times. Abbreviations: DCC, dicyclohexylcarbodiimide; DCM, dichloromethane; DIEA, N,N-diisopropylethylamine, DMF, dimethylformamide; HOBt, 1-hydroxybenzotriazole; TFA, trifluoroacetic acid. The sulfate ester containing peptides of formula (1) thus prepared may be desalted and purified by the usual methods. For example, the product may be purified by ion-exchange chromatography with use of Trisacryl M DEAE, DEAE-cellulose or the like, partition chromatography with use of Sephadex LH-20, Sephadex G-25 or the like, reverse phase chromatography with use of Amberlite XAD-2, ODS-silica gel or the like, normal phase chromatography with use of silica gel or the like, or high-performance liquid chromatography (HPLC). Analogous procedures, wherein the reactions are carried out without the solid phase component (resin), are well known in the art and well suited to large scale production. [See, e.g., U.S. Patent 3,892,726.] Utility The peptides of this invention have the ability to inhibit feeding activity in mammals. As a result they have utility in the prevention and treatment of obesity. Feeding inhibition activity can be demonstrated in rats as follows: Male Sprague-Dawley rats (weighing 300-350 g) are individually caged and maintained on a 12 hr light, dark cycle and trained for at least 14 days to feed during a three hr period of the dark cycle but not the 21 hours preceding that three hr period. The day of the study, rats are dosed intraperitoneally with saline (controls) or test compound (dissolved in saline; usually at a concentration of 0.3 to 300 micrograms of test compound per kg of rat weight). Food is introduced 10 minutes after administration of saline or test compound. Test compounds are deemed to be active if the test group consumes significantly less food than the saline controls during the feeding period which ends either 0.5 or 3 hr after presentation of food. The % feeding inhibition for the 0.5 hr feeding period obtained by administering a dose of 30 µg/kg of test compound is given in Table 2 for CCK-8 and various compounds of the invention. An appropriate procedure for administering a peptide designated here as suitable for intraperitoneal, intravenous, intramuscular, subcutaneous, or intranasal administration, to a mammal in need of either treatment for obesity or prevention of obesity, is at a dose of about 0.3 micrograms (µg) to 3 mg per kg of body weight per day, either as single dose or divided among two to four doses. The dosage may be varied, depending upon the requirements of the patient and the compound being employed. EXAMPLES The invention may be further illustrated by the following examples. Examples 1-18 illustrate the synthesis of intermediates. Examples 19- 42 illustrate the synthesis of compounds that have been designated above as either a compound of the invention or a compound useful in the treatment and prevention of obesity. The examples are intended to illustrate the invention, not to limit it in any manner. Peptide syntheses, unless otherwise stated, were initiated with 1 milliequivalent of aminomethyl resin, where the resin was 99:1 by weight styrene:divinylbenzene copolymer. Reactions were performed at room temperature unless otherwise stated. Washing steps were performed three times with 50 ml of the specified solvent unless otherwise stated. EXAMPLE 1 Isobutyl Succinimidyl Carbonate (iBuOCO-OSu) To a solution of isobutyl chloroformate (26 ml, 200 mmole) in 600 ml of chloroform was added in portions the dicyclohexylamine (DCHA) salt of N-hydroxysuccinimide (HOSu, 49.28 g, 200 mmole). After stirring the resulting suspension overnight, the precipitated DCHA hydrochloride was filtered off and washed with chloroform. The concentrated filtrate (ca. 50 ml) and washings were diluted with 400 ml of ethyl acetate (EtOAc) and washed with 10% citric acid (4 x 100 ml), brine (2 x 100 ml), 10% sodium bicarbonate (3 x 100 ml), and brine (4 x 100 ml) and then dried (magnesium sulfate), filtered, and concentrated to ca. 100 ml. On diluting with ether and precipitating with hexane, 26.6 g (62% yield) of iBuOCO-OSu was obtained, mp 33-35°C. EXAMPLE 2 Fmoc-DTyr-OH D-Tyrosine (1.81 g) was dissolved in 20 ml of water and 30 ml of tetrahydrofuran (THF) with 10 ml of N sodium hydroxide. Solid 9-fluorenylmethyl succinimidyl carbonate (Fmoc-OSu, 3.37 g) was added with rapid stirring. The suspension was adjusted to pH 7 with N sodium hydroxide and stirred overnight. Solid citric acid (3 g) was added followed by 60 ml of EtOAc. The EtOAc layer was collected, washed with 10% citric acid, brine, and dried (magnesium sulfate). Evaporation of the EtOAc solution gave a light tan syrup which was crystallized from dichloromethane (DCM) to give 3.9 g of Fmoc-DTyr-OH, mp 178-181°C. EXAMPLE 3 Fmoc-Tyr-OH Following the procedure of Example 2 but substituting L-tyrosine (9.06 g) for D-tyrosine, 18.4 g of Fmoc-Tyr-OH was obtained, mp 172-177°C. EXAMPLE 4 Fmoc-MeTyr-OH Following the procedure of Example 2 but substituting N-methyltyrosine (1.95 g) for D-tyrosine, 1.22 g of Fmoc-MeTyr-OH was obtained, mp 152-158°C. EXAMPLE 5 Boc-MePhe-(4-oxymethylphenyl)acetic Acid To a solution of Boc-MePhe-OH (27.93 g) and 4-(bromomethyl) phenylacetic acid phenacyl ester (33.32 g) in 1000 ml of acetonitrile was added potassium fluoride dihydrate (18.28 g). The suspension was stirred overnight, filtered and the filtrate evaporated to dryness. The residue, Boc-MePhe-(4-oxymethylphenyl)acetic acid phenacyl ester, was dissolved in 85% acetic acid (1200 ml), treated with zinc dust (128 g), and stirred for 2-4 hrs. Concentration of the filtered reaction mixture to ca. 400 ml and dilution with ca. 3200 ml of water gave an oil which was dissolved in EtOAc and treated with DCHA to give 41.31 g of the DCHA salt of title compound, mp 120-122°C. EXAMPLE 6 Boc-EtPhe-(4-oxymethylphenyl)acetic Acid Following the procedure of Example 5 but substituting Boc-EtPhe-OH (7.33 g) for Boc-MePhe-OH, 5.69 g of the DCHA salt of Boc-EtPhe-(4-oxymethylphenyl)acetic acid was obtained, mp 137-141°C. EXAMPLE 7 Boc-Phe(4-Cl)-(4-oxymethylphenyl)acetic Acid Following the procedure of Example 5 but substituting Boc-Phe(4-Cl)-OH (2.5 g) for Boc-MePhe-OH, 3.44 g of the free base of Boc-Phe(4-Cl)-(4-oxymethylphenyl)acetic acid was obtained. EXAMPLE 8 Boc-Tyr(Me)-(4-oxymethylphenyl)acetic Acid Following the procedure of Example 5 but substituting Boc-Tyr(Me)-OH (2.5 g) for Boc-MePhe-OH, 1.83 g of the free base of Boc-Tyr(Me)-(4-oxymethylphenyl)acetic acid was obtained, mp 64-67°C. EXAMPLE 9 Fmoc-Tyr(tBu)-(4-oxymethylphenyl)acetic Acid Following the procedure of Example 5 but substituting Fmoc-Tyr(tBu)-OH (6.86 g) for Boc-MePhe-OH, 4.88 g of the free base of Fmoc-Tyr(tBu)-(4-oxymethylphenyl)acetic acid was obtained, mp 192-195°C. EXAMPLE 10 Fmoc-Met-Asp(OtBu)-OH Fmoc-Met-OSu was prepared, in situ, by the reaction of Fmoc-Met-OH (14.87 g), HOSu (5.52 g), and dicyclohexylcarbodiimide (DCC, 8.26 g) in THF (200 ml) at 0°C for 3.5 hrs. Precipitated dicyclohexylurea (DCU) was removed by filtration and the THF filtrate was added to a cold solution of H-Asp (OtBu)-OH in 220 ml of 10:1 water/THF to which had been added 40 ml of N sodium hydroxide. After stirring the reaction mixture at room temperature overnight, solid citric acid (20 g) was added along with EtOAc (600 ml). The EtOAc layer was separated, washed with 10% citric acid and brine, and dried (magnesium sulfate). Evaporation of the EtOAc solution gave a residue which was dissolved in 200 ml of EtOAc and treated with DCHA (7.84 ml) to precipitate 17.93 g of the DCHA salt of the desired product, mp 159-162°C. EXAMPLE 11 H-Phe-OCH₂-Pam-resin Boc-Phe-(4-oxymethylphenyl)acetic acid (0.83 g, 2 mmole), 1-hydroxybenzotriazole (HOBt, 0.46 g, 3 mmole) and DCC (0.41 g, 2 mmole) were dissolved in 50 ml of 4:1 DCM/DMF and stirred at 0°C for 1 hr. Aminomethyl-resin (1.34 g, 1 mmole available nitrogen (was suspended in the filtered reaction mixture (precipitated DCU removed) and shaken for 2 to 15 hours. The product, Boc-Phe-OCH₂-Pam-resin, was isolated by filtration and treated according to Table 1 (Steps 10-14) to give the desired free base, H-Phe-OCH₂-Pam-resin. EXAMPLE 12 H-MePhe-OCH₂-Pam-resin Boc-MePhe-(4-oxymethylphenyl)acetic acid (from 1.82 g, 3 mmole, of its DCHA salt, Example 5) and HOBt (0.69 g, 4.5 mmole) in 40 ml of 1:3 DMF/DCM followed by DCC (0.62 g, 3 mmole) in 20 ml of DCM were added to aminomethyl-resin (1.34 g, 1 mmole available nitrogen) to give a suspension which was shaken for 2 to 15 hours. The desired product, Boc-MePhe-OCH₂-Pam-resin, was isolated by filtration, washed with 2-propanol and DCM, and treated according to Table 1 (Steps 10-14) to give the desired free base, H-MePhe-OCH₂-Pam-resin. EXAMPLE 13 H-EtPhe-OCH₂-Pam-resin Following the procedure of Example 12 but substituting Boc-EtPhe-(4-oxymethylphenyl)acetic acid (from 1.87 g, 3 mmole, of its DCHA salt, Example 6) for Boc-MePhe-(4-oxymethylphenyl)acetic acid, H-EtPhe-OCH₂-Pam-resin was obtained. EXAMPLE 14 H-Phe(4-Cl)-OCH₂-Pam-resin Following the procedure of Example 11 but substituting Boc-Phe(4-Cl)-(4-oxymethylphenyl)acetic acid (0.90 g, 2 mmole, Example 7) for Boc-Phe-(4-oxymethylphenyl)acetic acid, H-Phe(4-Cl)-OCH₂-Pam-resin was obtained. EXAMPLE 15 H-Phe(4-NO₂)-OCH₂-Pam-resin Boc-Phe(4-NO₂)-OH (1.39 g) was dissolved in 100 ml of 70% methanol (MeOH) and adjusted to pH 7 with the addition of N cesium bicarbonate. The solution was evaporated to dryness with the residue being evaporated three more times with added DMF. The resultant dried cesium salt of Boc-Phe(4-NO₂)-OH was dissolved in 60 ml of DMF and shaken with BrCH₂-Pam-resin (1 meq or Br) overnight. The desired product, Boc-Phe(4-NO₂)-OCH₂-Pam-resin, was isolated by filtration, washed with DCM, and treated according to Table 1 (Steps 10-14) to give the desired free base, H-Phe(4-NO₂)-OCH₂-Pam-resin. EXAMPLE 16 H-Tyr(Me)-OCH₂Pam-resin Following the procedure of Example 11 but substituting Boc-Tyr(Me)-(4-oxymethylphenyl)acetic acid (0.87 g, 2 mmole, Example 8) for Boc-Phe-(4-oxymethylphenyl)acetic acid, H-Tyr(Me)-OCH₂-Pam-resin was obtained. EXAMPLE 17 H-Tyr(tBu)-OCH₂-Pam-resin Fmoc-Tyr(tBu)-(4-oxymethylphenyl)acetic acid (1.82 g, 3 mmole, Example 9), 1-hydroxybenzotriazole (HOBt, 0.69 g, 4.5 mmole), and DCC (0.62 g, 3 mmole) were dissolved in 50 ml of 4:1 DCM/DMF and stirred at 0°C for 1 hr. Aminomethylresin (1.34 g, 1 mmole available nitrogen) was suspended in the filtered reaction mixture (precipitated DCU removed) and shaken for 2 to 15 hours. The product, Fmoc-Tyr(tBu)-OCH₂-Pam-resin, was isolated by filtration and treated according to Table 1 (Steps 16-20) to give the desired free base, H-Tyr (tBu)-OCH₂-Pam-resin. EXAMPLE 18 H-MeTyr(Me)-OCH₂-Pam-resin Following the procedure of Example 15 but substituting Boc-MeTyr(Me)-OH (from 1.47 g of its DCHA salt) for Boc-Phe(NO₂)-OH, H-MeTyr(Me)-OCH₂-Pam-resin was obtained. EXAMPLE 19 H-DAsp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) (JP-A-60-194 000), was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Met-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Met-OH, Fmoc-Tyr-OH (Example 3), and Fmoc-DAsp(OtBu)-OH according to Table 1 (coupling Steps 3-4 followed by Fmoc removal Steps 16-20) to provide Fmoc-DAsp(OtBu)-Tyr-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was sulfated, deprotected, and cleaved from the resin according to Table 1 (Steps 21-25, Steps 10-20, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Trisacryl M DEAE according to Table 1 (Step 30) to give 198 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 2.11 (2), Tyr 1.04 (1), Met 2.07 (2), Gly 1.08 (1), and Phe 1.04 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.35 (TLC herein refers to chromatography of the title compound on Merck silica gel thin layer plates in the solvent system chloroform-methanol-acetic acid-water, 6:3:1:1. EXAMPLE 20 iBuOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Met-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Met-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to give H-Tyr(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was coupled with iBuOCO-OSu (Example 1) according to Table 1 (Steps 8-9) to give iBuOCO-Tyr(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2, Trisacryl M DEAE, and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 206 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.06 (1), Tyr 1.04 (1), Met 2.04 (2), Gly 1.06 (1), and Phe 1.04 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.56. EXAMPLE 21 Suc-Tyr(SO₃H)-Ahx-Gly-Try-Ahx-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Ahx-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Ahx-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to give H-Tyr(tBu)-Ahx-Gly-Trp-Ahx-Asp(OtBu)-Phe-OCH₂-Pam-resin which was coupled with succinic anhydride (0.6 g, 6 mmole, in DMF) according to Table 1 (Steps 8-9) to give Suc-Tyr(tBu)-Ahx-Gly-Trp-Ahx-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2, Trisacryl M DEAE, and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 240 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.01 (1), Tyr 0.95 (1), Ahx 2.10 (2), Gly 1.06 (1), and Phe 0.88 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.36. EXAMPLE 22 H-βAsp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂ H-MePhe-OCH₂-Pam-resin (Example 12) was sequentially coupled with Fmoc-Met-Asp(OtBu)-OH (Example 10), Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Met-OH, Fmoc-Tyr(tBu)-OH, and Boc-βAsp(OtBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to give Boc-βAsp(OtBu)-Tyr(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was deprotected according to Table 1 (Steps 10-15) and coupled with Fmoc-OSu (1.1 g) according to Table 1 (Steps 8-9) to give Fmoc-βAsp-Tyr-Met-Gly-Trp-Met-Asp-MePhe-OCH2-Pam-resin which was sulfated deprotected, and cleaved from the resin according to Table 1 (Steps 21-25, Steps 16-20, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2, Trisacryl M DEAE, and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 72 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 2.03 (2), Tyr 1.05 (1), Met 1.85 (2), and Gly 1.10 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.33. EXAMPLE 23 H-DAsp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂ H-MePhe-OCH₂-Pam-resin (Example 12) was sequentially coupled with Fmoc-Met-Asp(OtBu)-OH (Example 10), Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Met-OH, Fmoc-Tyr(tBu)-OH, and Fmoc-DAsp(OtBu)-OH according to Table 1 (coupling Steps 3-4 followed by Fmoc removal Steps 16-20) to give Fmoc-DAsp(OtBu)-Tyr(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was deprotected, sulfated, deprotected, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, Steps 16-20, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Trisacryl M DEAE and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 110 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 2.01 (2), Tyr 1.01 (1), Met 1.91 (2), and Gly 1.07 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.35. EXAMPLE 24 For-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂ H-MePhe-OCH₂-Pam-resin (Example 12) was sequentially coupled with Fmoc-Met-Asp(OtBu)-OH (Example 10), Fmoc-Trp-OH, Fmoc-Gly-OH, and Fmoc-Met-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to give Fmoc-Met-Gly-Trp-Met-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was deprotected according to Table 1 (Steps 10-20) and coupled with For-Tyr-OH according to Table 1 (Steps 5-7) to give For-Tyr-Met-Gly-Trp-Met-Asp-MePhe-OCH₂-Pam-resin which was sulfated and cleaved from the resin according to Table 1 (Steps 21-25 and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2, Trisacryl M DEAE, and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 78 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.02 (1), Tyr 1.01 (1), Met 1.95 (2), and Gly 1.02 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.45. EXAMPLE 25 iBuOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂ H-MePhe-OCH₂-Pam-resin (Example 12) was sequentially coupled with Fmoc-Met-Asp(OtBu)-OH (Example 10), Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Met-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to give H-Tyr(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was coupled with iBuOCO-OSu (Example 1) according to Table 1 (Steps 8-9) to give iBuOCO-Tyr(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2, Trisacryl M DEAE, and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 302 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.03 (1), Tyr 1.02 (1), Met 1.91 (2), and Gly 1.04 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.67. EXAMPLE 26 Hpp(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂ H-MePhe-OCH₂-Pam-resin (Example 12) was sequentially coupled with Fmoc-Met-Asp(OtBu)-OH (Example 10), Fmoc-Trp-OH, Fmoc-Gly-OH, and Fmoc-Met-OH according to Table 1 (coupling Steps 3-4 followed by Fmoc removal Steps 16-20) to give H-Met-Gly-Trp-Met-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was coupled with 3-(4-hydroxyphenyl)propionic acid N-hydroxysuccinimide ester (Hpp-OSu) according to Table 1 (Steps 8-9) to give Hpp-Met-Gly-Trp-Met-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Trisacryl M DEAE and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 170 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.02 (1), Met 1.97 (2), and Gly 1.01 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.58. EXAMPLE 27 PrOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Met-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Met-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to give H-Tyr-(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was coupled with PrOCO-OSu (mp 31-34°C, prepared according to the procedure of Example 1 except that propyl chloroformate was substituted for isobutyl chloroformate) according to Table 1 (Steps 8-9) to give PrOCO-Tyr(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2 and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 270 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.01 (1), Tyr 1.03 (1), Met 1.87 (2), Gly 1.02 (1), and Phe 1.06 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.45. EXAMPLE 28 EtOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Met-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Met-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to give H-Tyr-(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was coupled with EtOCO-OSu (mp 52-54.5°C, prepared according to the procedure of Example 1 except that ethyl chloroformate was substituted for isobutyl chloroformate) according to Table 1 (Steps 8-9) to give EtOCO-Tyr(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2 and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 300 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.02 (1), Tyr 1.01 (1), Met 1.91 (2), Gly 1.02 (1), and Phe 1.04 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.44. EXAMPLE 29 MeOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Met-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Met-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to give H-Tyr-(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was coupled with MeOCO-OSu (mp 87-89°C, prepared according to the procedure of Example 1 except that methyl chloroformate was substituted for isobutyl chloroformate) according to Table 1 (Steps 8-9) to give MeOCO-Tyr(tBu)-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2 and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 270 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.04 (1), Tyr 1.05 (1), Met 1.82 (2), Gly 1.03 (1), and Phe 1.06 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.44. EXAMPLE 30 H-βAsp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂ The title compound has previously been prepared (Digestive Diseases, 15 , 149-156 (1970)). H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Met-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Met-OH, Fmoc-Tyr-OH (Example 3), and Boc-βAsp(OtBu)-OH according to Table 1 (coupling Steps 3-4 followed by Fmoc removal Steps 16-20) to provide Boc-βAsp(OtBu)-Tyr-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was sulfated, deprotected, and cleaved from the resin according to Table 1 (Steps 21-25, Steps 10-15, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Trisacryl M DEAE according to Table 1 (Step 30) to give 283 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 2.03 (2), Tyr 0.94 (1), Met 2.08 (2), Gly 0.99 (1), and Phe 0.96 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.52. EXAMPLE 31 Suc-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂ The title compound has previously been prepared (European Patent Application 0107860). H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Met-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Met-OH, and Fmoc-Tyr-OH (Example 3) according to Table 1 (coupling Steps 3-4 followed by Fmoc removal Steps 16-20) to provide H-Tyr-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was coupled with succinic anhydride in DMF according to Table 1 (Steps 8-9) to give Suc-Try-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was sulfated, deprotected, and cleaved from the resin according to Table 1 (Steps 21-25, Steps 10-15, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Trisacryl M DEAE according to Table 1 (Step 30) to give 246 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.03 (1), Tyr 0.95 (1), Met 2.08 (2), Gly 0.98 (1), and Phe 0.96 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.54. EXAMPLE 32 Hpp(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂ The title compound has previously been prepared (Int. J. Peptide Protein Res., 16 , 402-411 (1980)). H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Met-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, and Fmoc-Met-OH according to Table 1 (coupling Steps 3-4 followed by Fmoc removal Steps 16-20) to provide H-Met-Gly-Trp-Met-Asp (OtBu)-Phe-OCH₂-Pam-resin which was coupled with Hpp-OSu in DMF according to Table 1 (Step 8-9) to give Hpp-Met-Gly-Trp-Met-Asp (OtBu)-Phe-OCH₂-Pam-resin which was sulfated, deprotected, and cleaved from the resin according to Table 1 (Steps 21-25, Steps 10-15, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Trisacryl M DEAE according to Table 1 (Step 30) to give 65 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.04 (1), Met 2.04 (2), Gly 0.95 (1), and Phe 1.00 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.47. EXAMPLE 33 For-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂ The title compound has previously been prepared (U.S. Patent 3,705,140). H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Met-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, and Fmoc-Met-OH according to Table 1 (coupling Steps 3-4 followed by Fmoc removal Steps 16-20) to provide H-Met-Gly-Trp-Met-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected according to Table 1 (Steps 10-15) to provide H-Met-Gly-Trp-Met-Asp-Phe-OCH₂-Pam-resin which was coupled with For-Tyr-OH according to Table 1 (Step 3-4) to give For-Tyr-Met-Gly-Trp-Met-Asp-Phe-OCH₂-Pam-resin which was sulfated and cleaved from the resin according to Table 1 (Steps 21-25 and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Trisacryl M DEAE and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 30 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Asp 1.00 (1), Met 1.98 (2), Gly 1.07 (1), and Phe 1.00 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.37. EXAMPLE 34 Suc-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-MePhe-NH₂ H-MePhe-OCH₂-Pam-resin (Example 12) was sequentially coupled with Fmoc-Ahx-Asp(OtBu)-OH (Example 10, Fmoc-Met-OH replaced with Fmoc-Ahx-OH), Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Ahx-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to provide H-Tyr(tBu)-Ahx-Gly-Trp-Ahx-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was coupled with succinic anhydride in DMF according to Table 1 (Steps 8-9) to give Suc-Tyr(tBu)-Ahx-Gly-Trp-Ahx-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2, Trisacryl M DEAE, and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 100 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Tyr 0.97 (1), Gly 1.00 (1), and Asp 1.00 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.46. EXAMPLE 35 iBuOCO-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-MePhe-NH₂ H-MePhe-OCH₂-Pam-resin (Example 12) was sequentially coupled with Fmoc-Ahx-Asp(OtBu)-OH (Example 10, Fmoc-Met-OH replaced with Fmoc-Ahx-OH), Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Ahx-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to provide H-Tyr(tBu)-Ahx-Gly-Trp-Ahx-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was coupled with iBuOCO-OSu (EXAMPLE 1) in DMF according to Table 1 (Steps 8-9) to give iBuOCO-Tyr(tBu)-Ahx-Gly-Trp-Ahx-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2 and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 290 mg of the ammonium salt of the title compound. Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.54. EXAMPLE 36 Hpp(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-MePhe-NH₂ H-MePhe-OCH₂-Pam-resin (Example 12) was sequentially coupled with Fmoc-Ahx-Asp(OtBu)-OH (Example 10, Fmoc-Met-OH replaced with Fmoc-Ahx-OH), Fmoc-Trp-OH, Fmoc-Gly-OH, and Fmoc-Ahx-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to provide H-Ahx-Gly-Trp-Ahx-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was coupled with Hpp-OSu in DMF according to Table 1 (Steps 8-9) to give Hpp-Ahx-Gly-Trp-Ahx-Asp(OtBu)-MePhe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2, Trisacryl M DEAE, and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 91 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Ahx 1.92 (2), Gly 1.03 (1), and Asp 1.05 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.40. EXAMPLE 37 iBuOCO-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Ahx-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Ahx-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to provide H-Tyr(tBu)-Ahx-Gly-Trp-Ahx-Asp(OtBu)-Phe-OCH₂-Pam-resin which was coupled with iBuOCO-OSu (Example 1) in DMF according to Table 1 (Steps 8-9) to give iBuOCO-Tyr(tBu)-Ahx-Gly-Trp-Ahx-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2 and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 800 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Tyr 0.90 (1), Ahx 1.84 (2), Gly 1.12(1), Asp 1.12 (1), and Phe 0.92 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.58. EXAMPLE 38 Hpp(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Asp(OtBu)-OH, Fmoc-Ahx-OH, Fmoc-Trp-OH, Fmoc-Gly-OH, and Fmoc-Ahx-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to provide H-Ahx-Gly-Trp-Ahx-Asp-(OtBu)-Phe-OCH₂-Pam-resin which was coupled with Hpp-OSu in DMF according to Table 1 (Step 8-9) to give Hpp-Ahx-Gly-Trp-Ahx-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2 and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 450 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Ahx 1.92 (2), Gly 1.01(1), Asp 1.10(1), and Phe 0.97(1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.47. EXAMPLE 39 For-Tyr(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Ile-Asp(OtBu)-OH (Example 10, Fmoc-Met-OH replaced with Fmoc-Ile-OH), Fmoc-Trp-OH, Fmoc-Gly-OH, and Fmoc-Ile-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to provide H-Ile-Gly-Trp-Ile-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected according to Table 1 (Steps 10-15) to provide H-Ile-Gly-Trp-Ile-Asp-Phe-OCH₂-Pam-resin which was coupled with For-Tyr-OH according to Table 1 (Steps 3-4) to give For-Tyr-Ile-Gly-Trp-Ile-Asp-Phe-OCH₂-Pam-resin which was sulfated and cleaved from the resin according to Table 1 (Steps 21-25 and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2 and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 200 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Tyr 0.98 (1), Ile 1.94 (2), Gly 1.00 (1), Asp 1.09 (1), and Phe 0.98 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.59. EXAMPLE 40 Suc-Tyr(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Ile-Asp(OtBu)-OH (Example 10, Fmoc-Met-OH replaced with Fmoc-Ile-OH), Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Ile-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to provide H-Tyr(tBu)-Ile-Gly-Trp-Ile-Asp(OtBu)-Phe-OCH₂-Pam-resin which was coupled with succinic anhydride in DMF according to Table 1 (Steps 8-9) to give Suc-Tyr(tBu)-Ile-Gly-Trp-Ile-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2 and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 300 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Tyr 1.00 (1), Ile 2.07 (2), Gly 0.97 (1), Asp 0.97 (1), and Phe 0.99 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.42. EXAMPLE 41 iBuOCO-Tyr(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Ile-Asp(OtBu)-OH (Example 10, Fmoc-Met-OH replaced with Fmoc-Ile-OH), Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Ile-OH, and Fmoc-Tyr(tBu)-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to provide H-Tyr(tBu)-Ile-Gly-Trp-Ile-Asp(OtBu)-Phe-OCH₂-Pam-resin which was coupled with iBuOCO-OSu (Example 1) in DMF according to Table 1 (Steps 8-9) to give iBuOCO-Tyr(tBu)-Ile-Gly-Trp-Ile-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amberlite XAD-2 and p-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 390 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Tyr 1.07 (1), Ile 2.21 (2), Gly 1.04 (1), Asp 1.00 (1), and Phe 1.03 (1). Infrared absorption spectrum showed a strong peak typical of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.61. EXAMPLE 42 Hpp(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂ H-Phe-OCH₂-Pam-resin (Example 11) was sequentially coupled with Fmoc-Ile-Asp(OtBu)-OH (Example 10, Fmoc-Met-OH replaced with Fmoc-Ile-OH), Fmoc-Trp-OH, Fmoc-Gly-OH, and Fmoc-Ile-OH according to Table 1 (coupling Steps 5-7 followed by Fmoc removal Steps 16-20) to provide H-Ile-Gly-Trp-Ile-Asp(OtBu)-Phe-OCH₂-Pam-resin which was coupled with Hpp-OSu in DMF according to Table 1 (Step 8-9) to give Hpp-Ile-Gly-Trp-Ile-Asp(OtBu)-Phe-OCH₂-Pam-resin which was deprotected, sulfated, and cleaved from the resin according to Table 1 (Steps 10-15, Steps 21-25, and then Steps 26-29 with ammonia) to give the title compound which was chromatographically purified on Amber lite XAD-2 and P-40 ODS-3, sequentially, according to Table 1 (Step 30) to give 280 mg of the ammonium salt of the title compound. Amino acid analysis following acid decomposition gave Ile 2.04 (2), Gly 0.99 (1), Asp 0.98 (1), and Phe 0.99 (1). Infrared absorption spectrum showed a strong peak typica of a sulfuric acid ester at 1050 cm⁻¹. TLC R f 0.52.

Claims: Claims for the following Contracting States : BE, CH, LI, DE, FR, GB, IT, LU, NL, SE A peptide of the formula wherein Q is H-βAsp, H-DAsp, For, Ac, Suc, desQ or R¹R²CHOCO; Y is H, (S)-NH or (S)-R³N; M is Met, Ahx, Leu or Ile; X is Met, Ahx, Leu or Ile; J is Asp, DAsp or MeAsp; F¹ is (S)-NH or (S)-R⁴N; R¹ and R² independently represent H or lower alkyl; R³ and R⁴ represent lower alkyl; and pharmaceutically acceptable salts thereof; provided that: (1) Q is desQ when Y is H; (2) Q is not Ac if, in the same peptide: Y is (S)-NH; M is Met, Ahx or Leu; X is Met, Ahx or Leu; J is Asp; and F¹ is (S)-NH; (3) Q is neither H-βAsp nor For if, in the same peptide: Y is (S)-NH; M is Met, Ahx or Leu; X is Met, Ahx or Leu; J is Asp; and F¹ is (S)-NH; (4) Y is not H if, in the same peptide: M is Met; X is Met; J is Asp; and F¹ is (S)-NH; (5) Q is not Suc if, in the same peptide: Y is (S)-NH; M is Met; X is Met; and J is Asp; and (6) Q is not H-DAsp if, in the same peptide: Y is (S)-NH; M is Met; X is Met; J is Asp; and F¹ is (S)-NH. A peptide as claimed in claim 1, which is iBuOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is Suc-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is H-βAsp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is H-DAsp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is For-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is iBuOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is Hpp(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is PrOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is EtOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is MeOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is Suc-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is iBuOCO-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is Hpp(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is iBuOCO-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is Hpp(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is For-Tyr(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is Suc-Tyr(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is iBuOCO-Tyr(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A peptide as claimed in claim 1, which is Hpp(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A composition for preventing obesity comprising a peptide as defined in claim 1, but without provisos (2)-(6). The use of a peptide as defined in claim 1, as a pharmaceutical. The use of a peptide as defined in claim 1, but without provisos (2)-(6), in the manufacture of a medicament for the treatment of obesity. A method of improving the bodily appearance of a human being which comprises administering to that human being intraperitoneally, intravenously, intramuscularly, subcutaneously or intranasally a peptide as defined in claim 1, but without provisos (2)-(6), or a pharmaceutically acceptable salt thereof, until a cosmetically beneficial loss of body weight has occurred. A process for the production of a peptide as defined in claim 1 by the solid phase method of sequential addition (followed by deprotection after each addition) of the requisite protected amino acid or protected oligopeptide to an amino-acyl resin of the formula wherein F¹ is as defined in claim 1, to afford a protected peptidyl resin of the formula wherein Pg is a suitable protecting group and Q, Y, M, X, J and F¹ are as defined in claim 1, which is sulphated, deprotected and treated with a methanolic amine. A process for the production of a peptide as defined in claim 1 by the solution phase method of sequential addition (followed by deprotection after each addition) of the requisite protected amino acid or protected oligopeptide to an amino-acyl amide of the formula wherein F¹ is as defined in claim 1, to afford a protected peptide amide of the formula wherein Pg is a suitable protecting group and Q, Y, M, X, J and F¹ are as defined in claim 1, which is sulphated and deprotected. Claims for the following Contracting States : AT, ES, GR, A process for preparation of a peptide of the formula wherein Q is H-βAsp, H-DAsp, For, Ac, Suc, desQ or R¹R²CHOCO; Y is H, (S)-NH or (S)-R³N; M is Met, Ahx, Leu or Ile; X is Met, Ahx, Leu or Ile; J is Asp, DAsp or MeAsp; F¹ is (S)-NH or (S)-R⁴N; R¹ and R² independently represent H or lower alkyl; R³ and R⁴ represent lower alkyl; and pharmaceutically acceptable salts thereof; provided that: (1) Q is desQ when Y is H; (2) Q is not Ac if, in the same peptide: Y is (S)-NH; M is Met, Ahx or Leu; X is Met, Ahx or Leu; J is Asp; and F¹ is (S)-NH; (3) Q is neither H-βAsp nor For if, in the same peptide: Y is (S)-NH; M is Met, Ahx or Leu; X is Met, Ahx or Leu; J is Asp; and F¹ is (S)-NH; (4) Y is not H if, in the same peptide: M is Met; X is Met; J is Asp; and F¹ is (S)-NH; (5) Q is not Suc if, in the same peptide: Y is (S)-NH; M is Met; X is Met; and J is Asp; and (6) Q is not H-DAsp if, in the same peptide: Y is (S)-NH; M is Met; X is Met; J is Asp; and F¹ is (S)-NH by the solid phase method of sequential addition (followed by deprotection after each addition) of the requisite protected amino acid or protected oligopeptide to an amino-acyl resin of the formula wherein F¹ is as defined above, to afford a protected peptidyl resin of the formula wherein Pg is a suitable protecting group and Q, Y, M, X, J and F¹ are as defined above, which is sulphated, deprotected and treated with a methanolic amine. A process for the production of a peptide of formula wherein Q is H-βAsp, H-DAsp, For, Ac, Suc, desQ or R¹R²CHOCO; Y is H, (S)-NH or (S)-R³N; M is Met, Ahx, Leu or Ile; X is Met, Ahx, Leu or Ile; J is Asp, DAsp or MeAsp; F¹ is (S)-NH or (S)-R⁴N; R¹ and R² independently represent H or lower alkyl; R³ and R⁴ represent lower alkyl; and pharmaceutically acceptable salts thereof; provided that: (1) Q is desQ when Y is H; (2) Q is not Ac if, in the same peptide: Y is (S)-NH; M is Met, Ahx or Leu; X is Met, Ahx or Leu; J is Asp; and F¹ is (S)-NH; (3) Q is neither H-βAsp nor For if, in the same peptide: Y is (S)-NH; M is Met, Ahx or Leu; X is Met, Ahx or Leu; J is Asp; and F¹ is (S)-NH; (4) Y is not H if, in the same peptide: M is Met; X is Met; J is Asp; and F¹ is (S)-NH; (5) Q is not Suc if, in the same peptide: Y is (S)-NH; M is Met; X is Met; and J is Asp; and (6) Q is not H-DAsp if, in the same peptide: Y is (S)-NH; M is Met; X is Met; J is Asp; and F¹ is (S)-NH by the solution phase method of sequential addition (followed by deprotection after each addition) of the requisite protected amino acid or protected oligopeptide to an amino-acyl amide of the formula wherein F¹ is as defined above, to afford a protected peptide amide of the formula wherein Pg is a suitable protecting group and Q, Y, M, X, J and F¹ are as defined above, which is sulphated and deprotected. A process, according to claim 1 or claim 2, wherein the peptide prepared is iBuOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is Suc-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is H-βAsp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is H-DAsp-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is For-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is iBuOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is Hpp(SO₃H)-Met-Gly-Trp-Met-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is PrOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is EtOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is MeOCO-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is Suc-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is iBuOCO-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is Hpp(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-MePhe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is iBuOCO-Tyr(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is Hpp(SO₃H)-Ahx-Gly-Trp-Ahx-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is For-Tyr(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is Suc-Tyr(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is iBuOCO-Tyr(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A process, according to claim 1 or claim 2, wherein the peptide prepared is Hpp(SO₃H)-Ile-Gly-Trp-Ile-Asp-Phe-NH₂, or a pharmaceutically acceptable salt thereof. A method of improving the bodily appearance of a human being which comprises administering to that human being intraperitoneally, intravenously, intramuscularly, subcutaneously or intranasally a peptide as defined in claim 1, but without provisos (2)-(6), or a pharmaceutically acceptable salt thereof, until a cosmetically beneficial loss of body weight has occurred.

Inventors: ROSAMOND JAMES DONALD, ROSAMOND, JAMES DONALD
Applicants: FISONS CORP, FISONS CORPORATION (A MASSACHUSETTS CORPORATION)
Application year: 1986
Main classification: C07K7
IPC codes: C07K14, A61P1, A61P3, C07K7, A61K38, C07K1