PEPTIDES CAPABLE OF CONTROLLING ACROSOME REACTION

Abstract: A pure DNA encoding a bombesin-like peptide which is capable of promoting acrosome reaction and the encoded peptide. Also disclosed are a vector and a cell containing such a DNA, a pharmaceutical composition which includes such a peptide, and a method of controlling fertilization using such a peptide or its agonist or antagonist.

Description: PEPTIDES CAPABLE OF CONTROLLING ACROSOME REACTION BACKGROUND OF THE INVENTION At present, the overall success rate for in vitro fertilization is approximately 20-25%. This figure includes multiple attempts (up to 3-4 times by some couples) to succeed. Thus, any process which can increase the efficiency of fertilization will have significant utility for in vitro fertilization procedures. On the other hand, it is estimated that there are 1.5 to 2 million pregnancies that occur in the United States alone because of failures in contraception. Failure rates of vaginal contraceptives such as foam or jelly, either alone or in combination with condoms or diaphragm, range from 2-20% per year depending on conditions and the study cited. See Developing New Contraceptive: Obstacles and Opportunities, Washington D.C., National Academy Press (1990). Therefore, any minor improvement in the efficiency of contraceptives, thousands of accidental or unwanted pregnancies could be prevented per year. Bo besin, a tetradecapeptide amide first isolated from the skin of the frog Bombina bombina, is a potent mitogen for mouse Swiss 3T3 fibroblast cells. It also stimulates secretion for guinea pig pancreatic acini. Bombesin-like peptides are produced and secreted by human small cell lung cancer cells ("SCLC") and exogenously added bombesin-like peptides can stimulate the growth of human SCLC cells in vitro . Two examples of bombesin-like peptides are gastrin releasing peptide ("GRP") and Neuromedin C. GRP is a 27 amino acid peptide amide first isolated from the porcine gut. The C-terminal amino acid sequence of GRP is almost identical to that of bombesin. Neuromedin C is a decapeptide amide, the structure of which is identical to the last ten amino acids in the C- terminal region of GRP. Both GRP and Neuromedin C share amino acid sequence homology with bombesin and possess bombesin-like properties. Other bombesin-like peptides include litorin and Neuromedin B. GRP is encoded by a gene located on the 18th chromosome. Naylor et al. Somat. Cell Mol. Genet. 13:87 (1987) . GRP is encoded by 3 exons with exon 1 encoding the first 23 amino acids of GRP and exon 2 the latter 4 amino acids. Spindel et al. Mol. Endocrinol. 1:224 (1987) . The GRP prohormone includes a signal peptide, the sequence of GRP, a dibasic amino acid cleavage site, and a long C-terminal peptide following the cleavage site. Bioactive GRP is processed from the prohormone basically in 3 steps; first by removal of the signal peptide, second by cleavage of the C-terminal peptide at the dibasic site, and third by amidation of GRP. GRP itself may then be further cleaved to give the C-terminal decapeptide of GRP (GRP-10) which has similar bioactivity as does GRP. For fertilization to occur, sperm must undergo an exocytotic process called the acrosome reaction which enables sperm to penetrate the external layers of the ova. It has not been reported hitherto that bombesin or bombesin-like peptides are capable of increasing or decreasing the efficiency of fertilization of eggs by sperm by promoting acrosome reaction. Uncommon Abbreviations: Chx-Ala = 3-cyclohexylalanine pGlu = pyroglutamic acid Nle = norleucine HyPro = hydroxyproline Ho oPro = homoproline (4 methylene units in the ring) Sar = sarcosine Aza-Tyr = 3-(5-hydroxy-2-pyridyl)-alanine Cpa = p-chlorophenylalanine X-Phe = p-, o-, or m- substituted phenylalanine F 5 -Phe = pentafluorophenylalanine Nal = 3-(naphthyl)-alanine Met-oxide = methionine oxide 1- or 3-methyl-His = histidine with a methyl substituent at N 1 or N 3 of its heterocyclic ring. Tec = l,2,3,4-tetrahydro-2-carboline-3-carboxylic acid Tic = l,2,3,4-tetrahydro-2-carboline-3-yl-carboxylic acid Tip = 4,5,6,7-tetrahydro-lH-imidazo[c]pyridine-6- carboxylic acid Oic = (3aS,7aS)-octahydroindol-2-yl-carboxylic acid Lys(Z) = N 6 -(benzyloxycarbonyl)-lysine Lys(COCH 3 ) = N 6 -acetyllysine Lys(COPh) = N 6 -benzoyllysine Lys(COCH 2 Ph) = N 6 -(phenylacetyl)-lysine Lys(COCH 2 CH 2 Ph) = N 6 -(3-phenylpropionyl)-lysine Sta (statine) = (3S,4S) -4-amino-3-hydroxy-6- methylheptanoic acid AHPPA = (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid ACHPA = (3S, 4S) -4-amino-5-cyclohexyl-3-hydroxypentanoic acid SUMMARY OF THE INVENTION For the acrosome reaction to occur, sperm must undergo the process of capacitation. (The operational definition of capacitation is simply the ability of sperm to undergo the acrosome reaction.) Applicants have now discovered that bombesin or its agonist/antagonist is capable of promoting/inhibiting the acrosome reaction, and that mRNA encoding a new bombesin-like peptide capable of stimulating the acrosome reaction arises from an alternate transcript of the GRP gene. Thus, one aspect of the present invention features a pure DNA encoding a peptide which is capable of promoting the acrosome reaction and identified herein as SEQ ID NO: 1, SEQ ID NO: 2 , SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6. Preferably, the DNA of this invention consists essentially of a nucleotide sequence identified herein as SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12. Also within this invention is a vector or a cell containing one of the above-described DNA sequences. Preferably, in a cell which contains the DNA of the invention, the DNA is introduced into the cell in a manner allowing the cell to express the peptide. The present invention further features a pure peptide identified herein as SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6. A pharmaceutical composition which includes one of the above-described peptides and a pharmaceutically acceptable carrier is an additional feature of the present invention. A still another feature of the present invention is a method of promoting fertilization. The method includes the step of contacting sperm either at the time of sperm capacitation or at the time of egg fertilization with an effective amount of one of the above-described peptides. Note that for fertilization to occur, sperm must undergo an exocytotic process called the acrosome reaction which enables sperm to penetrate the external layers of the ova. For the acrosome reaction to occur, sperm must undergo the process of capacitation. The operational definition of capacitation is simply the ability of sperm to undergo the acrosome reaction. It is a further feature of the present invention to prepare one of the above-described peptides by a DNA recombinant method which includes the steps of (i) introducing a DNA encoding the peptide into cells in a manner allowing the cells to express the peptide; (ii) culturing the cells in a medium; and (iii) recovering the expressed peptide. What is meant by "pure DNA" herein is DNA that is not immediately contiguous with both of the coding sequences with which it is immediately contiguous (i.e., one at the 5' end and one at the 3' end) in the naturally-occurring genome of the organism from which the DNA of the invention is derived. The term therefore includes, for example, a recombinant DNA which is incorporated into a vector; into an autonomously replicating plasmid or virus; or into the genomic DNA of a prokaryote or eukaryote, or which exists as a separate molecule (e.g., a cDNA or a genomic DNA fragment produced by polymerase chain reaction or restriction endonuclease treatment) independent of other DNA sequences. It also includes a recombinant DNA which is part of a hybrid gene encoding additional polypeptide sequence. A pure peptide, on the other hand, is a peptide which is free or substantially free of the components with which it naturally occurs. Another aspect of the present invention relates to a method of controlling fertilization by contacting sperm either at the time of sperm capacitation or at the time of egg fertilization with an effective amount of bombesin or its agonist/antagonist capable of stimulating/inhibiting the acrosome reaction. The method can be applied to in vitro fertilization or artificial insemination for promoting fertilization. For example, bombesin or a suitable bombesin agonist [e.g., bombesin (6-14), GRP, or GRP (18- 27)] can be administered vaginally to a female subject, or administered systemically or locally to a male subject. Local administration to a male subject can be achieved by implantation of a biodegradable or retrievable polymer formulation in the scrotum. An example of a suitable biodegradable polymer for such use is polylactide-glycolide polymer carrier. E.g., see Tissier B. Recent Progress on GnRH and Gonadal Peptides, pp. 159-168, Bouchard P. et al. eds. Elsevier, Paris (1990) . Silicone, on the other hand, can be used to prepare a retrivable polymer formulation to be implanted in a male subject. Note the term "subject" herein refers to either a human being or an animal. In other words, both medical and veterinary applications are within the scope of the present invention. The method can also be used to block fertilization by administering vaginally to a female subject a suitable bombesin antagonist, e.g., in a formulation consisting of sponge, foam, jelly, and a biocompatible matrix (such as a barrier type of contraceptive device) . Alternatively, the bombesin antagonist can be administered to a male subject, either systemically or locally. The dose of bombesin or its agonist or antagonist used according to the present invention varies depending upon the manner of administration and the condition of the subject to be treated, and ultimately will be decided by the attending physician or veterinarian. Such amount of the active peptide compound as determined by the attending physician or veterinarian is referred to herein as an "effective amount". A typical administration method is oral administration or parenteral administration. The structure of bombesin is as follows: H-pGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly -His- Leu-Met-NH 2 (SEQ ID NO: 20). The structure of GRP is as follows: H-Ala-Pro-Val-Ser-Val-Gly-Gly-Gly-Thr-Val-Leu-Ala- Lys-Met-Tyr-Pro-Arg-Gly-Asn-His-Trp-Ala-Val-Gly-His- Leu-Met-NH 2 (SEQ ID NO: 21) . A bombesin agonist of this invention refers to any compound which shows a biological activity similar to that of bombesin, e.g., GRP. A bombesin antagonist of this invention, on the other hand, refers to a compound which blocks the biological activity of bombesin. Examples of bombesin agonists and antagonists include, but are not limited to, bombesin fragments [e.g., bombesin (6-14)], GRP, GRP fragments [e.g., GRP (18-27)], and numerous synthetic compounds disclosed in the art including the publications to be discussed immediately below [e.g., Tpi 6 , Leu 13 -ψ(CH 2 -NH)-Leu 14 bombesin (6-14)]. (Note that ψ stands for a pseudopeptide bond and the type of the bond is indicated in the parenthesis following it.) Naturally occurring compounds such as Neuromedin B or Neuromedin C, either in human or in other organisms, are also included. Several bombesin antagonists are known whereby the structure of the undecapeptide, substance P, is modified by the replacement of several of its L-amino acids with D-amino acids. See Jensen et al. Nature 309:61 (1984); Zachary et al. Proc. Natl. Acad. Sci. USA 82:7616 (1985); and Heinz-Erian et al. Gastroenterology 90:1455 (1986). A few bombesin antagonists derived from the structure of bombesin have also been disclosed. See Markl et al. Peptides 2, Suppl. 2:169 (1981) and Heinz-Erian et al. Amer. J. Physiol. 252:G439 (1987). In addition, it has been disclosed that bombesin antagonists containing a pseudopeptide bond, e.g., [Leu 13 -ψ(CH 2 -NH)-Leu 14 ]bombesin and Ala 9 -ψ(CH 2 -NH)-Val 10 -Leu 14 ]bombesin, are also bombesin antagonists. See Coy et al. Regulatory Peptides 19:105 (1987) ; International Symposium on Bombesin-like Peptides, Rome, October, 1987; and Coy et al. J. Biol. Chem. 263:5056 (1988). Furthermore, certain Neuromedin C derivatives have been found to be potent bombesin antagonists. See EP Application 0 345 990 A2 (1989) . Several bombesin agonists are disclosed in Wang et al. J. Biol. Chem. 265:15695 (1990). All of the just-mentioned articles and the publications listed below contain bombesin agonists and antagonists which can be used to practice the present invention. Coy et al. Peptides, Proceedings of the Eleventh Amer. Peptide Symposium, Ed. by Rivier et al. ESCOM, pp. 65-67 (1990); Wang et al. J. Biol. Chem. 265:15695 (1990); Mahmoud et al. Cancer Research 51:1798 (1991); Wang et al. Biochemistry 29:616 (1990); Heimbrook et al., "Synthetic Peptides: Approaches to Biological Problems", UCLA Symposium on Mol. and Cell. Biol. New Series, Vol. 86, ed. Tam and Kaiser; Martinez et al., J. Med. Chem. 28:1874 (1985); Gargosky et al., Biochem. J. 247:427 (1987); Dubreuil et al., Drug Design and Delivery, Vol 2:49, Harwood Academic Publishers, GB (1987); Heikkila et al., J. Biol. Chem. 262:16456 (1987); Caranikas et al., J. Med. Chem. 25:1313 (1982); Saeed et al., Peptides 10:597 (1989); Rosell et al.. Trends in Pharmacological Sciences 3:211 (1982); Lundberg et al., Proc. Nat. Aca. Sci. 80:1120, (1983); Engberg et al.. Nature 293:222 (1984); Mizrahi et al., Euro. J. Pharma. 82:101 (1982); Leander et al., Nature 294:467 (1981); Woll et al., Biochem. Biophys. Res. Comm. 155:359 (1988); Rivier et al., Biochem. 17:1766 (1978); Cuttitta et al., Cancer Surveys 4:707 (1985); Aumelas et al., Int. J. Peptide Res. 30:596 (1987) ; Szepeshazi. et al., Cancer Resaerch 51:5980 (1991); Jensen, et al. Trends Pharmacol. Sci. 12:13 (1991); U.S. Patent No. 5,028,692; U.S. Patent No. 4,943,561; U.S. Patent No. 4,207,311; U.S. Patent No. 5,068,222; U.S. Patent No. 5,081,107; U.S. Patent No. 5,084,555; EP Application 0 315 367 A2 (1989) EP Application 0 434 979 Al (1991) EP Application 0 468 497 A2 (1992) EP Application 0 313 158 A2 (1989) EP Application 0 339 193 Al (1989) PCT Application WO 90/01037 (1990) PCT Application WO 90/02545 (1992); and UK Application GB 1 231 051 A (1990). Preferably, the bombesin agonist of this invention has the following formula: wherein A 1 is a D-amino acid selected from the group consisting of Phe and X-Phe (where X is F, Cl, Br, N0 2 , OH, or CH 3 ) , Tec, Tic, Tip, or Oic, or is deleted; A 2 is Gin, His, 1-methyl-His, or 3-methyl-His; A 3 is a D- or L-amino acid selected from the group consisting of 3-Nal, Trp, Phe, and X-Phe, where X is F, Cl, Br, N0 2 , OH, or CH 3 ; A 4 is Ala, Val, Leu, lie, Nle, or α-aminobutyric acid; A 5 is Val, Ala, Leu, lie, Nle, Thr, or α- a inobutyric acid; A 6 is Gly, Sar, or a D-amino acid selected from the group consisting of Ala, N-methyl-Ala, Trp, and β- Nal; A 7 is His, 1-methyl-His, or 3-methyl-His; A 8 is Leu, lie, Val, Nle, α-aminobutyric acid, Trp, 0-Nal, Chx-Ala, Phe, or X-Phe, where X is F, Cl, Br, N0 2 , OH, or CH 3 ; A 9 is Met, Met-oxide, Leu, lie, Nle, α- aminobutyric acid, or Cys; each R 1 and R 2 , independently, is H, C-^ Q alkyl, 2 - 20 alkenyl c 2 - 20 alkynyl, phenyl, naphthyl, η_ 20 phenylalkyl, C 11 _ 20 naphthylalkyl, COEi or COOE ! (where E- is C 1 _ 20 alkyl, C 2 _ 20 alkenyl, C 2 _ 20 alkynyl, phenyl, naphthyl, C 7 _ 20 phenylalkyl, C 11 _ 20 naphthylalkyl, pyridyl, or indolyl) ; provided that when either R x or R 2 is COE i or COOE-^ the other must be H; and R 3 is OH, NH 2 , C- ^20 alkoxy, C 7 _ 20 phenylalkoxy, or C 1;L --. 20 naphthylalkoxy. Particular preferred agonists covered by formula (A) are those in which A 1 is D-Phe, D-Cpa, or deleted; A 2 is Gin, His, 1-methyl-His, or 3-methyl-His; A 3 is Trp; A 4 is Ala; A 5 is Val; A 6 is Sar, Gly, D-Phe, or D-Ala; A 7 is His, Lys(Z), Lys(COCH 3 ), Lys(COPh), Lys(COCH 2 Ph) , or Lys(COCH 2 CH 2 Ph) ; A 8 is Leu, Phe, Chx-Ala, or Cys; and A 9 is Met, Leu, lie, Nle, or Cys. Also preferably, the bombesin antagonist of this invention has the following formula: wherein A 0 is pGlu, Gly, Nle, α-aminobutyric acid, a D-isomer selected from the group consisting of Ala, Val, Gin, Asn, Leu, lie. Met, Phe, X-Phe (where X is F, Cl, Br, N0 2 , OH, or CH 3 ) , Trp, Cys and Nal, or deleted; A 1 is a D or L-isomer selected from the group consisting of pGlu, Nle and α-aminobutyric acid, a D-isomer selected from the group consisting of Ala, Val, Gin, Asn, Leu, lie, Met, Phe, X-Phe (where X is F, Cl, Br, N0 2 , OH, or CH 3 ) , F 5 -Phe, Aza-Tyr, Trp, Nal, Pro, HyPro, homoPro, Tic, Tec, Tip, Oic and Cys, or deleted; A 2 is pGlu, Gly, Ala, Val, Gin, Asn, Leu, lie, Met, Phe, X-Phe (where X is F, Cl, Br, N0 2 , OH, or CH 3 ) , Trp, Cys, Nal, His, 1-methyl-His, or 3-methyl-His; A 4 is Ala, Val, Gin, Asn, Gly, Leu, lie, Nle, α-aminobutyric acid, Met, Phe, X-Phe (where X is F, Cl, Br, N0 2 , OH, or CH 3 ) , Trp, Cys, or Nal; A 5 is Gin, Asn, Gly, Ala, Leu, lie, Nle, α-aminobutyric acid, Met, Val, Phe, X-Phe (where X is F, Cl, Br, OH, or CH 3 ) , Trp, Thr, or Nal; A 6 is Sar, Gly, or a D-isomer selected from the group consisting of Ala, N-methyl-Ala, Val, Gin, Asn, Leu, lie, Met, Phe, X-Phe (where X is F, Cl, Br, N0 2 , OH, or CH 3 ) , Trp, Cys and or Nal; A 7 is 1-methyl-His, 3-methyl-His, or His; each R 1 and R 2 , independently, is H, C 1 _ 20 alkyl, C 2 _ 20 alkenyl, C 2 _ 20 alkynyl, phenyl, naphthyl, C η _ 2Q phenylalkyl, C 1;1 _ 20 naphthylalkyl, COE ! or COOE (where E 2 is C 1 _ 20 alkyl, C 3 _ 20 alkenyl, C-J^ alkynyl, phenyl, naphthyl, C 7 _ 20 phenylalkyl, C^.^ naphthylalkyl, pyridyl, or indolyl) , and is bonded to the nitrogen of the «-amino group of the N-terminal amino acid residue; W can be any one of the following: (I): wherein R 3 is CHR 20 -(CH 2 ) n (where R 20 is either of H or OH; and n is either of 1 or 0) , or is deleted, and Z 2 is the identifying group of an amino acid selected from the group consisting Gly, Ala, Val, Leu, lie, Ser, Asp, Asn, Glu, Gin, Phe, X-Phe (where X is F, Cl, Br, N0 2 , OH, or CH 3 ) , F 5 -Phe, Trp, Cys, Met, Pro, HyPro, ChxAla and Nal; and V x is either OR 4 , or R 5 N X where R 4 is R 4 is C 1 _ 20 alkyl, C^^ alkenyl, C 3 _ 20 alkynyl, phenyl, naphthyl, C 7 _ 20 phenylalkyl, C 11 _ 20 naphthylalkyl and each R 5 and R 6 , independently, is H, C 1 _ 20 alkyl, C 3 _ 20 alkenyl, C 3 _ 20 alkynyl, phenyl, naphthyl, C 7 _ 20 phenylalkyl, C 11 _ 20 naphthylalkyl, m. _ 2 Q ac yl or . R-- / ' where R 7 is H, C 1 _ 20 alkyl, C _ 2Q alkenyl, C 3 _ 20 alkynyl, phenyl, naphthyl, C^o phenylalkyl, C 13 _ 20 naphthylalkyl, or C^o acyl; provided that, when either R 5 or R 6 is -NHR 22 , the other is H; (II): 8 2 3 -N-CH-R 9 -CH-C-V 2 , wherein R 9 is CH 2 -NH, CH 2 -S, CH 2 -0, CH 2 -S(0)', CH 2 -S(0) π , CO-CH 2 , CH 2 -CO, or CH 2 -CH 2 , and each Z and Z 3 , independently, is the identifying group of an amino acid selected from the group consisting of Gly, Ala, Val, Leu, lie, Ser, Asp, Asn, Glu, Gin, Nal, Phe, X-Phe (where X is F, Cl, Br, N0 2 , OH or CH 3 ) , F 5 -Phe, Trp, Cys, Met, Pro, HyPro, homoPro, Tic, Tec, Tip, Oic and ChxAla; and V 2 is either OR 10 or ^11 N. \ R 12 where each R 8 , R 10 , R 1X , and R 12 , independently, is H, C λ _ 2 o alkyl, C 2 _ 20 alkenyl, C 2 _ 20 alkynyl, phenyl, naphthyl, c 7 - 20 phenylalkyl, or C^.^ naphthylalkyl; (III): wherein Z is the identifying group of an amino acid selected from the group consisting of Gly, Ala, Val, Leu, lie, Ser, Asp, Asn, Glu, Nal, Gin, Phe, X-Phe (where X is F, Cl, Br, N0 2 , OH or CH 3 ) , F 5 -Phe, Trp, Cys, Met, Pro and HyPro; and each R 13 , R 14 , and R 15 , independently, is H, C x _ 2 o alkyl, C 2 _ 20 alkenyl, C 2 _ 2 o alkynyl, phenyl, naphthyl, C 7 _ 20 phenylalkyl, or C- ..^ naphthylalkyl; or (IV) : wherein each R 16 and R 17 , independently, is H, 0 2 . 20 alkyl, C 2 _ 2 o alkenyl, C 2 _ 2 o alkynyl, phenyl, naphthyl, C 7 _ 20 phenylalkyl, or C 11 _ 20 naphthylalkyl; provided that, if A 0 is present, A 1 cannot be pGlu; further provided that, if A 0 or A 1 is present, A 2 cannot be pGlu; further provided that, when A 0 is deleted and A 1 is pGlu, j must be H and R 2 must be the portion of Glu that forms the imine ring in pGlu; further provided that when one of R 1 or R 2 is COE, the other must be H; further provided that if Z 2 is the identifying group of Pro, HyPro, Tic, Tec, Tip or Oic, R 8 is a bond linking Z 2 and the nitrogen in R 8 -N; further provided that if Z 3 is the identifying group of Pro, HyPro, ho oPro, Tic, Tec, Tip or Oic, R 9 must be CH 2 -N with its nitrogen bonded to Z 3 ; or a pharmaceutically acceptable salt thereof. By "pseudopeptide bond" is meant that the carbon atom participating in the bond between two residues is reduced from a carbonyl carbon to a methylene carbon, i.e., CH -NH; or, less preferably, that CO-NH is replaced with any of CH 2 -S, CH 2 -0, CH 2 -S(0) 1 , CH 2 -S(0) π , CH 2 -CH 2 , CH 2 -CO, or CO-CH 2 . [A detailed discussion of the chemistry of pseudopeptide bonds is given in Coy et al., Tetrahedron 44.,3:835-841 (1988); Tourwe (1985) Janssen Chim. Acta 2:3-15, 17-18; and Spatola (1983) in Chemistry and Biochemistry of Amino Acids, Peptides, and Proteins, (B. Weinstein, ed.) M. Dekker, New York and Basel, pp. 267-357.] One modification of the naturally occurring peptide to create an analog administered according to the invention is of the amino terminal end of the molecule, such as those described for the amino terminal positions in the generic formula (B) above; for example, the N-terminal amino acid residue, which is A 0 or, if A 0 is deleted, is A 1 or, if A 0 and A 1 are deleted, is A 2 , may be an aromatic D-isomer, or may be an alkylated amino acid residue. (Where "D" is not designated as the configuration of an amino acid, L is intended.) Particularly preferred antagonists covered by formula (B) are those in which W is (I) ; or in which A 0 is Gly, D-Phe, or deleted; A 1 is p-Glu, F 5 -Phe, Aza-Tyr, D-Phe, D-Ala, D-3-Nal, D-Cpa, or D-Asn; A 2 is Gin, His, 1-methyl-His, or 3-methyl-His; A 4 is Ala; A 5 is Val; A 6 is Sar, Gly, D-Phe, or D-Ala; A 7 is His, Lys(Z), Lys(COCH 3 ), Lys(COPh), Lys(COCH 2 Ph) , or Lys(COCH 2 CH 2 Ph) ; and. W is (I), and R 3 is CH 2 -CH 2 , CH 2 , or deleted and Z 1 is the identifying group of Leu or Phe; W is (I) , and R 3 is CHOH-CH 2 , Z- γ is the identifying group of Leu, Chx-Ala, or Phe and each R 5 and R 6 , independently, is H; W is (I) , and v 1 is NHR 6 in which R 6 is NH 2 ; W is (II), and R 9 is CH 2 -NH and each Z 2 and Z 3 , independently, is the identifying group of Leu or Phe; W is (III) , and Z 4 is the identifying group of Leu, Phe, X-Phe (where X is F, Cl, Br, N0 2 , OH, or CH 3 ) and each R 13 , R 14 and R 15 , independently, is H, C- - 2Q alkyl, C 2 _ 20 alkenyl, C 2 _ 2 o alkynyl, phenyl, naphthyl, C 7 _ 2Q phenylalkyl, or C _ 2 o naphthylalkyl; or W is (IV) , and each R 16 and R 17 , independently, is H and each R 1 and R 2 , independently, is H, C i . 20 alkyl, COE- ^ , or COOE^ Preferably, (1) W is (I), and R 3 is CH 2 -CH 2 , CH 2 , or deleted and Z 1 is the identifying group of Leu or Phe; (2) W is (I), and R 3 is CHOH-CH 2 , Z is the identifying group of Leu, Chx-Ala, or Phe, and each R 5 and R 6 , independently, is H; (3) W is (I), and V is NHR 6 in which R 5 is NH 2 ; (4) W is (II), and R g is CH 2 -NH and each Z 2 and Z 3 , independently, is the identifying group of Leu or Phe; (5) W is (III) , and Z 4 is the identifying group of Leu, Phe, or X-Phe (where X is F, Cl, Br, N0 2 , OH, or CH 3 ) and each R 13 , R 14 and R 15 , independently, is H, C l . 20 alkyl, C 2 _ 2 o alkenyl, C 2 _ 20 alkynyl, phenyl, naphthyl, C 7 _ 20 phenylalkyl, or C^.J Q naphthylalkyl; and (6) W is (IV) , and each R 16 and R 17 , independently, is H and each and R 2 , independently, is H, C-^ Q alkyl, COE^ or COOE ! . Particularly preferred antagonists are those in which W is (I), R 3 is CH 2 -CH 2 , CH 2 , or deleted, Z λ is the identifying group of Leu or Phe, V λ is NHR 6 and R 6 is is H, C 1 _ 20 alkyl, Cη__ 20 phenylalkyl, or C^ Q acyl, e.g., D- Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NH(C 3 H 7 ) . It is also preferred that the bombesin antagonist of this invention have the following formula: wherein A 1 is D- or L-pGlu, or is deleted; A 2 is Gin, Asn, Gly, Ala, Leu, lie, Nle, α- aminobutyric acid, Met, Val, Phe, p-X-Phe (where X is F, Cl, Br, OH or CH 3 ) , Trp, 0-naphthylalanine, or is deleted; A 3 is D- or L-Arg, D- or L-Lys, or is deleted; A 4 is Gin, Asn, Gly, Ala, Leu, lie, Nle, α- aminobutyric acid, Met, Val, Phe, p-X-Phe (where X is F, Cl, Br, OH or CH 3 ) , Trp, 0-naphtylalanine, or is deleted; A 5 is a D- or L-amino acid selected from the group consisting of Gin, Asn, Gly, Ala, Leu, lie, Nle, α- aminobutyric acid, Met, Val, Phe, p-X-Phe (where X is F, Cl, Br, OH or CH 3 ) , Trp, and 0-naphthylalanine, or is deleted; A 6 is a D- or L-amino acid selected from the group consisting of Gin, Asn, Gly, Ala, N-Ac-Ala, Leu, lie, Nle, α-aminobutyric acid, Met, Val, Phe, p-X-Phe (where X is F, Cl, Br, OH or CH 3 ) , Trp, p-Glu, Sar, and β- naphthylalanine, or is deleted; A 7 is Gin, Asn, Gly, Ala, Leu, lie, Nle, α- aminobutyric acid, Met, Val, D- or L-Phe, p-X-Phe (where X is F, Cl, Br, OH or CH 3 ) , Trp, Lys, His, or β- naphthylalanine; A 8 is Trp or Met; A 9 is a D- or L-amino acid selected from the group consisting of Gin, Asn, Gly, Ala, Leu, lie, Nle, α- aminobutyric acid. Met, Val, Phe, p-X-Phe (where X is F, Cl, Br, OH or CH 3 ) , Trp, and ,9-naphthylalanine; A 10 is Gin, Asn, Gly, Ala, Leu, lie, Nle, α- aminobutyric acid, Met, Val, Phe, p-X-Phe (where X is F, Cl, Br, OH or CH 3 ) , Trp, Thr, or ,5-naphthylalanine; A 11 is a D- or L-amino acid selected from the group consisting of Gly, Ala and Phe; A 12 is a D- or L-amino acid selected from the group consisting of His, Phe, and p-X-Phe (where X is F, Cl, Br, OH, CH 3 ) ; A 13 is Gin, Asn, Gly, Ala, Leu, lie, Nle, α- aminobutyric acid, Met, Val, Phe, p-X-Phe (where X is F, Cl, Br, OH or CH 3 ) , Trp, or 3-naphthylalanine; A 14 is Gin, Asn, Gly, Ala, Leu, lie, Nle, α- aminobutyric acid, Met, Val, Phe, p-X-Phe (where X is F, Cl, Br, OH or CH 3 ) , Trp, or 3-naphthylalanine; each R 1# R 2 , R 3 and R 4 , independently, is H, C λ _ 20 alkyl, C 2 _ 20 alkenyl, C 2 _ 2 o alkynyl, phenyl, naphthyl, Cτ_ 20 phenylalkyl, C lλ _ 20 naphthylalkyl, COE α , or COOE^ ^ (where E χ is C 1 _ 20 alkyl, C 2 _ 20 alkenyl, C 2 _ 20 alkynyl, phenyl, naphthyl, C 7 _ 20 phenylalkyl, C 11 _ 2Q naphthylalkyl, pyridyl, or indolyl) ; provided that when either R 1 or R 2 is COE ! or COOE 1# the other must be H and when either R 3 or R 4 is COE j or COOE^ the other must be H; further provided that pGlu can only be a N-terminal residue and that when the N-terminal residue is pGlu, R 2 is H and R 2 is a bond linking the nitrogen of the «-amino group and the carbon of the γ-carboxyl group of pGlu; further provided that for each of the residues A 7 , A 8 , A 9 , A 11 , A 12 , and A 13 , independently, the carbon atom participating in the amide bond between that residue and the nitrogen atom of the α-amino group of the adjacent amino acid residue may be a carbonyl carbon or may be reduced to a methylene carbon. Particularly preferred antagonists covered by formula (C) are those in which A 1 through A 6 are deleted, A 13 is Leu, A 14 is Leu, and the carbon atom participating in the amide bond between A 3 and A 14 is a methylene carbon. Note that except for tethered amino acids (e.g., Pro or Tic) , a three-letter abbreviation of an amino acid and A 1 , A 2 or the like herein stands for an amino acid residue, i.e., =N-CH(R)-CO- when it is at the N-termi-.us and -NH-CH(R)-CO- when it is not at the N-terminus, where R denotes the identifying group (i.e., side chain) of an amino acid or its residue, e.g., R is CH 2 COOH for Asp. The symbol Pro stands for the structure of -NC CO-. Other tethered amino acids are denoted in an analogous manner. Also, where the amino acid residue is optically active, it is the L-form configuration that is intended unless D-form is expressly designated. COE ! stands for O 0 -C-E and COOE- ^ for -C-O-E^ HyPro herein refers to any of 2-hydroxy-Pro, 3-hydroxy-Pro, 4-hydroxy-Pro, and 5- hydroxy-Pro; 4-hydroxy-Pro is preferred. Other features and advantages of the invention will be apparent from the following description and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS The drawings are first briefly described. Fig. 1 is a sequence and translation of a rhesus monkey cDNA encoding peptides capable of promoting acrosome reaction. Fig. 2 is a schematic representation of the mechanism by which a mRNA encoding acrosome reaction- promoting peptides is produced in human testes. Fig. 3 is a graph showing distribution of mRNA encoding acrosome reaction-promoting peptides by polymerase chain reaction. Fig. 4 is a sequence and translation of a human cDNA encoding peptides capable of promoting acrosome reaction. Fig. 5 is a graph showing effect of bombesin on induction of acrosome reaction. Fig. 6 is a graph showing effect of the bombesin analog D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NH(C 3 H 7 ) (code name: BIM 26147) on bombesin or progesterone induced acrosome reaction in human and monkey sperm. Closed and open bars stand for use of BIM 26147 and blank control, respectively. DESCRIPTION OF THE PREFERRED EMBODIMENTS Cloning/Identification of a DNA Sequence Encoding a New Bombesin-Related Peptide High levels of mRNA that hybridizes to the human GRP cDNA were found to be present in monkey testes. Northern blot analysis clearly shows that GRP mRNA present in monkey testes in higher concentrations than in non-neoplastic tissue such as lung. In addition, in situ hybridization has clearly localized the GRP mRNA to developing sperm. Sequence analysis of partial cDNA clones (which lacked the 5'-end of the mRNA and the coding region for the bombesin-like peptide) derived from a monkey testes cDNA library shows that the hybridizing monkey mRNA is clearly related to human GRP. Furthermore, hybridization study suggests that the 5'-end of this mRNA may be different from that of GRP and could thus encode a new bombesin-like peptide (i.e., other than GRP). Described below is the procedures used by us to successfully clone a mRNA from monkey testes which encodes such a new peptide. A cDNA probe for exon 3 of monkey GRP was first generated by the following method. (The structure of the monkey GRP gene, including designation of exons, is provided below.) Two 17-base oligonucleotides corresponding to sequences in exon 3 of monkey GRP, i.e., GTAGACTCTCTGCTCCAG (SEQ ID NO: 15) and AAACCAGAAGATGCTGCT (SEQ ID NO: 16) , were used to amplify the corresponding DNA sequence from rhesus monkey genomic DNA by the polymerase chain reaction ("PCR") . The sequence of the 5'-terminal segment of the probe is shown in Fig. 1 (in dashed box) . The monkey genomic DNA was purchased from a commercial source (Clonetech, Palo Alto, California) . PCR conditions were 35 cycles of 1 min. at 92°C, 2 min. at 55°C, 2 min. at 72°C. The resulting band was subcloned into the vector Bluescriptll (Stratagene, La Jolla, California) following standard procedures as described by Ausubel et al. Current Protocols in Molecular Biology, John Wiley & Sons, New York (1987). The sequence of the subcloned DNA as monkey GRP exon 3 was confirmed by DNA sequence analysis using double-stranded template as described in Chen, E. Y. et al. , DNA 4:165 (1985) and flanking primers in the vector. The subcloned DNA was subsequently used to prepare a probe to screen a monkey testes cDNA library which was constructed as follows. Rhesus monkey testes were collected from sacrificed monkeys. Total RNA was prepared using guanidine thiocyanate and CsCl ultracentrifugation as described in Chirgwin J. M. et al. Biochemistry 18:5294 (1979). Poly(A) RNA was prepared using oligo (dT) cellulose. See Ausubel et al. id . A cDNA library was prepared in the vector λZapII using reagents and protocols supplied by Stratagene (UniZap Cloning Kit) as described previously. Nagalla, S. R. et al. J. Biol. Chem. 267:6916 (1992). The library, which contained greater than 2xl0 6 independent clones with an average insert size of 1-1.5 kb, was plated, transferred to nitrocellulose, UV cross- linked, and screened with the monkey GRP exon 3 probe. For library screening, the probe was prepared as a 32 p- labeled antisense cRNA probe using the T7RNA polymerase promoter present in the vector. Hybridization conditions were 50% formamide/5x SSC/5x Denhardt's/50 mM sodium phosphate, pH 7.0/2.5% SDS/200 μg/ml sonicated denatured salmon sperm/200 μg yeast RNA at 42° for 18 hr. Blots were washed for two 15 min. intervals in 2x SSC/0.1% SDS at 50°. Approximately 45 hybridizing clones were identified. Some of the hybridizing clones were plaque purified and the cDNA inserts were excised into the vector bluescript using helper phage (following Stratagene protocol) . Plasmid DNA was prepared according to standard methods [Ausubel et al. id . ] and sequenced as described above. The nucleotide sequence of the monkey cDNA thus obtained, as well as the deduced amino acid sequence, is shown in Fig. 1. Because mRNA corresponding to the Fig. 1 cDNA has been identified in spermatocytes and the new bombesin-like peptides encoded by it play a role in the acrosome reaction, the new peptides are designated herein acrosome-related peptides ("ARP's"). In Fig. 1, the sequence of the probe used to identify ARP's is indicated by a dashed box, and the sites of intron-exon boundaries based on homology with the human GRP gene (Spindel et al., id . ) are indicated by solid triangles. The probe used to identify the ARP cDNA lies in exon 3. The C-terminal extension peptide of the ARP prohormone is encoded on exons 2 and 3, all but the C-terminal 4 amino acids of ARP's are encoded in exon A, and the C-terminal 4 amino acids of ARP's are encoded in exon 2. The above designation of exons in monkey GRP gene is identical to that for human GRP gene (see Fig. 2 and its accompanying text below) . In Fig. 1, the sequence encoding ARP's and the glycine for the carboxy-terminal amide are underlined. The C-terminal glycine serves as the amide donor for the C-terminal methionyl-a ide residue of an ARP's. Braάoury et al. Nature 298:686 (1982). The two dibasic cleavage sites, Lys-Arg and Lys-Lys, are overlined. Douglass et al. Annu. Rev. Biochem, 53:665 (1984). ARP's play an important role in regulating the efficiency of fertilization of eggs by sperm. Hence, the peptides themselves and their agonists can be used to promote fertilization. On the other hand, their antagonists have contraceptive utility. Based on the amino acid sequence of Fig. 1 and known active bombesin-like peptides (e.g., GRP), biologically active ARP's include the following (respective numbers of amino acid residues are given) : (1) Monkey ARP-27: H-Met-Leu-Val-Lys-Arg-Ala-Arg-Cys-Leu-Leu-Ser-Cys- His-Ala-Ser-Gly-Gln-Gly-Cys-Leu-Gly-Ile-Pro-Gly-His- Leu-Met-NH 2 (SEQ ID NO: 1) ; (2) Monkey ARP-22: H-Ala-Arg-Cys-Leu-Leu-Ser-Cys-His-Ala-Ser-Gly-Gln- Gly-Cys-Leu-Gly-Ile-Pro-Gly-His-Leu-Met-NH 2 (SEQ ID NO: 2) ; and (3) Monkey ARP-11: H-Gln-Gly-Cys-Leu-Gly-Ile-Pro-Gly-His-Leu-Met-NH 2 (SEQ ID NO: 3) . Monkey ARP-27, monkey ARP-22 and monkey ARP-11 are encoded by the following segments in the cDNA sequences in Fig. 1, respectively: ATGCTTGTGAAAAGGGCCAGGTGTCTTCTGTCTTGCCATGCAAGTGGGCAG GGCTGCTTGGGAATACCAGGGCACTTAATGGGG (SEQ ID NO: 7) ; GCCAGGTGTCTTCTGTCTTGCCATGCAAGTGGGCAGGGCTGCTTGGGAATA CCAGGGCACTTAATGGGG (SEQ ID NO: 8); and CAGGGCTGCTTGGGAATACCAGGGCACTTAATGGGG (SEQ ID NO: 9); The human GRP gene was cloned as described in Spindel et al. Mol. Endocrinol. 1:224 (1987). Sequence of the 5'-flanking region up to base -534 was obtained as described in that reference. Additional sequence was obtained by subcloning a Xmal-Xmal fragment corresponding to bases -1705 to -24 of the 5'-flanking region of the human GRP gene from the same genomic clone used in Spindel et al., id . This fragment was subcloned into the vector PGEM3 and sequenced as described by Chen et al., id . using flanking primers in the vector and internal primers from derived sequence.] The nucleotide sequence of all exons and some introns of the human GRP gene can be found in Fig. 2 of Spindel id . and Fig. 4 herein below. As will be discussed immediately below, DNA sequence consisting of the first 185 nucleotides in Fig. 4 is part of a newly found exon and corresponds to sequence -864 to -680 in Fig. 2, Spindel. et al. id . . Furthermore, the numbering system in Fig. 2 thereof is adopted for the human GRP gene throughout this disclosure. Comparison of the sequence of the monkey ARP cDNA with the sequence of the human GRP gene clearly indicates how ARP's arise from the human GRP gene and also explicitly predicts the amino acid sequences of human ARP's. More specifically, the sequence of the monkey ARP cDNA consisting of the first 185 nucleotides (Fig. 1) is nearly identical to bases -864 to -680 of the human GRP gene relative to the transcriptional start site as described by Spindel et al. id . The remainder of the cDNA sequence of monkey ARP's (from base 186 to the 3' end) is nearly identical to the segment covering base 248 to base 709 of the human GRP gene sequence. Base 248 corresponds to the beginning of exon 2 of the human GRP gene. Thus, the ARP mRNA arises by initiation of transcription of a hitherto unknown exon (named "exon A" herein) of the GRP gene at approximately 864 base upstream from the transcriptional start described in Spindel et al., id . , followed by splicing of this new exon into the previously described exons 2 and 3 of the GRP gene. See Fig. 2, which shows both a schematic representation of the structure of the human GRP gene (top) and mechanisms by which the GRP mRNA and the ARP mRNA are produced in different tissues. More specifically, while a standard transcriptional initiation site is used and exons 1, 2 and 3 of the GRP gene in most tissues are spliced together to produce GRP (see Spindel et al., id. ) , an upstream promoter is used to initiate transcription at approximately base -864 relative to the standard site of initiation in testes to produce a mRNA with an additional exon, exon A. Exon A is then spliced to exons 2 and 3, thereby giving the processed mRNA which encodes ARP's in testes. Note that determination of intron between exon A and exon 1 was based on decreased sequence homology between the monkey cDNA and human gene sequences, and the presence of an intron donor site consensus sequence (GTGGG) in the human GRP promoter sequence. As shown in Fig. 3, PCR analysis confirms the existence of the ARP mRNA in human testes. More specifically, RNA from the tissues shown above were reverse transcribed and then amplified by the PCR using a pair of primers that spanned exon A of the GRP gene, i.e., GTGTATGTGGCAGTTCAGGGA (SEQ ID NO: 17) and ATGGCAAGACAGAAGA (SEQ ID NO: 18) . Amplified DNA was separated by gel electrophoresis, transferred to nylon membranes and detected by hybridization to a probe corresponding to a sequence internal to the two primers used for amplification (i.e., TGCATGCTTGTGAAAAG (SEQ ID NO: 19) . The intensity of hybridization in human testes is similar to that observed in monkey testes. PCR analysis also indicates that ARP mRNA is expressed in cervix, oviduct, uterus, ovary and fetal lung. Thus, the ARP mRNA has a wide distribution in human tissues and its encoded peptides have a variety of physiologic and pathologic roles. These include effects on efficiency of fertilization of eggs by sperm as well as effects on the growth of neoplastic tissues and the regulation of gastrointestinal functions. The sequence and translation of the human ARP cDNA which is determined based on the close homology between the monkey and human DNA sequences are shown in Fig. 4. The sequence encoding the bioactive peptides and the glycine for the carboxy-terminal amide are underlined. The two dibasic cleavage sites (Lys-Arg and Lys-Lys) , on the other hand, are overlined. Thus, human ARP's have the following sequences which are highly homologous to their simian counterparts: (1) Human ARP-27: H-Met-Leu-Val-Lys-Arg-Ala-Ser-Tyr-Leu-Leu-Ser-Cys- His-Thr-Ser-Gly-Gln-Ser-Cys-Leu-Gly-Ile-Pro-Gly-His- Leu-Met-NH 2 (SEQ ID NO: 4); (2) Human ARP-22: H-Ala-Ser-Tyr-Leu-Leu-Ser-Cys-His-Thr-Ser-Gly-Gln- Ser-Cys-Leu-Gly-Ile-Pro-Gly-His-Leu-Met-NH 2 (SEQ ID NO: 5) ; and (3) Human ARP-11: H-Gln-Ser-Cys-Leu-Gly-Ile-Pro-Gly-His-Leu-Met- NH 2 (SEQ ID NO: 6) . Human ARP-27, human ARP-22 and human ARP-11 are encoded by the following segments in the cDNA sequences in Fig. 4, respectively: ATGCTTGTGAAAAGGGCCAGCTATCTTCTGTCTTGCCATACAAGTGGGCAG AGCTGCCTGGGAATACCAGGGCACTTAATGGGG (SEQ ID NO: 10); GCCAGCTATCTTCTGTCTTGCCATACAAGTGGGCAGAGCTGCCTGGGAATA CCAGGGCACTTAATGGGG (SEQ ID NO: 11); and CAGAGCTGCCTGGGAATACCAGGGCACTTAATGGGG (SEQ ID NO: 12) ; The presence of the ARP mRNA in both human and monkey testes suggested that ARP's, a newly discovered class of bombesin-like peptides, played a role in fertilization. Thus, it was proposed that bombesin, ARP's and other bombesin-like peptides had effects on the spontaneous acrosome reaction, which is necessary for sperm to fertilize the egg. Results from the experiments described below under the subheading "Effects of Bombesin Agonists/Antagonists on Acrosome Reaction" confirmed that proposition. Synthesis of Bombesin Agonists/Antagonists The synthesis of the bombesin analog pGlu-Gln-Trp-Ala-Val-Gly-His-Leu-ψ[CH 2 NH]-Leu-NH 2 (SEQ ID NO: 22) follows. Other bombesin analogs were prepared by making appropriate modifications of the following synthetic method. The first step was the preparation of the intermediate, pGlu-Gln-Trp-Ala-Val-Gly-His (benzyloxycarbonyl) -Leu-ψ[CH 2 NH]-Leu-benzhydrylamine resin, as follows. Benzhydrylamine-polystyrene resin (Vega Biochemicals, Inc.) (0.97 g, 0.5 mmole) in the chloride ion form was placed in the reaction vessel of a Beckman 99OB peptide synthesizer programmed to perform the following reaction cycle: (a) methylene chloride; (b) 33% trifluoroacetic acid (TFA) in methylene chloride (2 times for 1 and 25 min. each) ; (c) methylene chloride; (d) ethanol; (e) methylene chloride; and (f) 10% triethylamine in chloroform. The neutralized resin was stirred with «-t-butoxycarbonyl("BOC") -Leu and diisopropylcarbodiimide (1.5 mmole each) in methylene chloride for 1 hour, and the resulting amino acid resin was then cycled through steps (a) to (f) in the above wash program. BOC-Leu aldehyde (1.25 mmoles) , prepared by the method of Fehrentz and Castro, Synthesis, p. 676 (1983) , was dissolved in 5 ml of dry dimethylformamide (DMF) and added to the resin TFA salt suspension followed by the addition of 100 mg (2 mmoles) of sodium cyanoborohydride [Sasaki and Coy, Peptides £:119-121 (1987); Coy et al. , Id.]. After stirring for 1 hour, the resin mixture was found to be negative to ninhydrin reaction (1 min.), indicating complete derivatization of the free amino group. The following amino acids (1.5 mmole) were then coupled successively in the presence diisopropyl¬ carbodiimide (1.5 mmole), and the resulting amino acid resin was cycled through washing/deblocking steps (a) to (f) in the same procedure as above: BOC-His(benzyloxycarbonyl) , BOC-Gly (coupled as a 6 M excess of the p-nitro- phenylester) , BOC-Val, BOC-Ala, BOC-Trp, BOC-Gln (coupled as a 6 M excess of the p-nitrophenylester) , and pGlu. The completed resin was then washed with methanol and air dried. The resin described above (1.6 g, 0.5 mmole) was mixed with anisole (5 ml) and anhydrous hydrogen fluoride (35 ml) at 0°C and stirred for 45 min. Excess hydrogen fluoride was evaporated rapidly under a stream of dry nitrogen, and free peptide was precipitated and washed with ether. The crude peptide was dissolved in a minimum volume of 2 M acetic acid and eluted on a column (2.5 x 100 mm) of Sephadex G-25 (Pharmacia Fine Chemicals, Inc.). Fractions containing a major component by UV absorption and thin layer chromatography ("TLC") were then pooled, evaporated to a small volume and applied to a column (2.5 x 50 cm) of octadecylsilane-silica (Whatman LRP-1, 15-20 μm mesh size). The peptide was eluted with a linear gradient of 0-30% acetonitrile in 0.1% trifluoroacetic acid in water. Fractions were examined by TLC and analytical high performance liquid chromatography ("HPLC") and pooled to give maximum purity. Repeated lyophilization of the solution from water gives 60 mg of the product as a white, fluffy powder. The product was found to be homogeneous by HPLC and TLC. Amino acid analysis of an acid hydrolysate confirms the composition of the peptide. The presence of the Leu-ψ[CH 2 -NH]-Leu bond was demonstrated by fast atom bombardment mass spectrometry. pGlu-Gln-Trp-Ala-Val-Gly-His-Phe-ψ[CH 2 NH]-Leu-NH 2 (SEQ ID NO: 23), pGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val -Gly-D-Phe-Leu-Met-NH 2 , pGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp- Ala-Val-Gly-D-Phe-Leu-Leu-NH 2 , pGlu-Gln-Arg-Tyr-Gly- Asn-Gln-Trp-Ala-Val-Gly-D-Phe-Leu-Met-NH 2 , or other peptides were prepared in similar yields in an analogous fashion by appropriately modifying the above procedure. Solid phase synthesis of D-Phe-Gln-Trp-Ala- Val-Gly-His-Leu-ψ[CH 2 NH]-D-Phe-NH 2 , was carried out as follows: BOC-D-Phe-Gln-Trp-Ala-Val-Gly-His(tosyl)-Leu- ψ[CH NH]-D-Phe-benzhydrylamine resin was synthesized first. Benzhydrylamine-polystyrene resin (Advanced ChemTech, Inc.) (1.25 g, 0.5 mmole) in the chloride ion form was placed in the reaction vessel of an Advanced ChemTech ACT 200 peptide synthesizer programmed to perform the following reaction cycle: (a) methylene chloride; (b) 33% trifluoroacetic acid in methylene chloride (2 times for 1 and 25 min. each) ; (c) methylene chloride; (d) ethanol; (e) methylene chloride; (f) 10% triethylamine in chloroform. The neutralized resin was stirred with BOC-D-phenylalanine and diisopropylcarbodiimide (1.5 mmole each) in methylene chloride for 1 hour and the resulting amino acid resin was then cycled through steps (a) to (g) in the above wash program. The BOC group was then removed by TFA treatment. BOC-Leu aldehyde (1.25 mmoles) , prepared by the method of Fehrentz and Castro, Id. , was dissolved in 5 ml of dry DMF and added to the resin TFA salt suspension followed by the addition of 100 mg (2 mmoles) of sodium cyanoborohydride. After stirring for 1 hour, the resin mixture was found to be negative to ninhydrin reaction (1 min.) indicating complete derivatization of the free amino group. The following amino acids (1.5 mmole) were then coupled successively by the same procedure: BOC-His(benzyloxycarbonyl) , BOC-Gly, BOC-Val, BOC-Ala, BOC-Trp, BOC-Gln (coupled in the presence of 1 equiv. hydroxybenzotriazole) , BOC-D-Phe (coupled in the presence of 1 equiv. hydroxybenzotriazole) . After drying, the peptide resin weighed 1.93 g. The resin (1.93 g, 0.5 mmole) was mixed with anisole (5 ml) and anhydrous hydrogen fluoride (35 ml) at 0°C and stirred for 45 min. Excess hydrogen fluoride was evaporated rapidly under a stream of dry nitrogen and free peptide precipitated and washed with ether. The crude peptide was dissolved in a minimum volume of 2 M acetic acid and eluted on a column (2.5 x 100 mm) of Sephadex G-25. Fractions containing a major component by UV absorption and TLC were then pooled, evaporated to a small volume and applied to a column (2.5 x 50 cm) of Vydac octadecylsilane (10-15 uM) . This was eluted with a linear gradient of 15-45% acetonitrile in 0.1% trifluoroacetic acid in water. Fractions were examined by TLC and analytical HPLC and pooled to give maximum purity. Repeated lyophilization of the solution from water gives 120 mg of the product as a white, fluffy powder. The product was found to be homogeneous by HPLC and TLC. Amino acid analysis of an acid hydrolysate confirms the composition of the peptide. The presence of the Leu-ψ[CH 2 NH] peptide bond was demonstrated by fast atom bombardment mass spectrometry. The analog D-Cpa-Gln-Trp-Ala-Val-Gly-His- Leu-ψ[CH 2 NH]-Phe-NH 2 (BIM 26159) may be synthesized in a similar manner by substituting D-Cpa for D-Phe. Solid phase synthesis of [D-Phe 1 , His 7 , desMet 9 ] Litorin, D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NH 2 , was carried out as follows. Step (1) : Benzhydrylamine-polystyrene resin (Advanced ChemTech, Inc. (0.62 gm, 0.25 mmole) in the chloride ion form was placed in the reaction vessel of an ACT 200 peptide synthesizer programmed to perform the following reaction cycle: (a) methylene chloride; (b) 33% trifluoroacetic acid in methylene chloride (2 times for 1 and 25 min. each) ; (c) methylene chloride; (d) ethanol; (e) methylene chloride; (f) 10% triethyla ine in chloroform. The neutralized resin was stirred with BOC-Leu and diisopropylcarbodiimide (1.5 mmole each) in methylene chloride for 1 hour and the resulting amino acid resin was then cycled through steps (a) to (f) in the above wash program. The following amino acids (1.5 mmole) were then coupled successively by the same procedure: BOC-His(benzyloxycarbonyl) , BOC-Gly, BOC-Val, BOC-Ala, BOC-Trp, BOC-Gln (coupled as a 6M excess of the p-nitrophenylester, and BOC-D-Phe (coupled in the presence of hydroxzybenzotriazole) . After drying, the peptide resin weighed 0.92 g. Step (2): The resin (0.92 g) was then mixed with anisole (5 ml) , dithiothreitol (200 mg) and anhydrous hydrogen fluoride (35 ml) at 0°C and stirred for 45 min. Excess hydrogen fluoride was evaporated rapidly under a stream of dry nitrogen and free peptide precipitated and washed with ether. The crude peptide was dissolved in a minimum volume of 2 M acetic acid and eluted on a column (2.5 x 100 cm) of Sephadex G-25. Fractions containing a major component by UV absorption and TLC were then pooled, evaporated to a small volume and applied to a column (2.5 x 50 cm) of Vydac octadecylsilane (10-15 micron) . The column was eluted with a linear gradient of 0-30% acetonitrile in 0.1% trifluoroacetic acid in water. Fractions were examined by TLC and pooled to give maximum purity. Repeated lyophilization of the solution from water gives a white, fluffy powder; this product was found to be homogeneous by HPLC and TLC. Amino acid analysis of an acid hydrolysate confirms the composition of the peptide. Synthesis of D-9-Nal-Gln-Trp-Ala-Val-Gly- His-Leu-NH 2 was accomplished using the same procedure as described above. Synthesis of N-acetyl-D-Phe-Gln-Trp-Ala-Val-Gly -His-Leu-NH 2 was accomplished using the same procedure as that described above, except that the final BOC group was removed and the resin acetylated with acetic anhydride in methylene chloride. The synthesis of [Sta 8 , desMet 9 ] Litorin follows. Sta is an abbreviation of statin or (3S, 4S)-4-amino- 3-hydroxy-6-methylheptanoic acid. A statin, AHPPA [i.e., (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid], or ACHPA [i.e., (3S, 4S) -4-amino-5-cyclohexyl-3- hydroxypentanoic acid] residue was substituted in place of any two amino acids of the analog, where the peptide contains only peptide bonds. For example, [Sta 8 , desMet 9 ] Litorin was prepared in an analogous fashion by first coupling statin to the resin and then proceeding with the addition of BOC-His(benzylocarbonyl) . Statine or BOC-statine was synthesized according to the method of Rich et al., 1978, J. Organic Chem. 43: 3624; and Rich et al., 1980, J. Med. Chem. 23.: 27, and AHPPA and ACHPA were synthesized according to the method of Hui et al., 1987, J. Med. Chem. 3_0: 1287; Schuda et al., 1988, J. Org. Chem. 53:873; and Rich et al., 1988, J. Org. Chem. 53:869. Solid-phase synthesis of the peptide pGlu-Gln-Trp- Ala-Val-Gly-His-Sta-NH 2 was accomplished through the use of the following procedures in which BOC-statine (prepared by the procedure of Rich et al., J. Org. Chem. 1978, 4_3, 3624) was first coupled to ethyl- benzhydrylamine-polystyrene resin. After acetylation, the intermediate p-Glu-Gln-Gln-Trp-Ala-Val-Gly- His(benzyloxycarbonyl)- Sta-methylbenzhydrylamine resin was prepared. The synthetic procedure used for this preparation follows in detail: 1. Incorporation of BOC-statine on methylbenzhydrylamine resin. Methylbenzhydrylamine-polystyrene resin (Vega Biochemicals, Inc.) (1.0 g, 0.73 mmol) in the chloride ion form was placed in the reaction vessel of a Vega 250C Coupler peptide synthesizer. The synthesizer was programmed to perform the following reactions: (a) methylene chloride; (b) 10% triethylamine in chloroform; (c) methylene chloride; and (d) dimethylformamide. The neutralized resin was mixed for 18 hours with the preformed active ester made from BOC-statine (1.46 mmol), diisopropyl carbodiimide (2 mmol), and hydroxybenzotriazole hydrate (1.46 mmol in dimethylformamide at 0°C. for one hour. The resulting amino acid resin was washed on the synthesizer with dimethylformamide and then methylene chloride. The resin mixture at this point was found by the Kaiser ninhydrin test (5 min.) to have an 84% level of statine incorporation on the resin. Acetylation was performed by mixing the amino acid- resin for 15 min. with N-acetyl imidazole (5 mmol) in methylene chloride. Derivatization to the 94-99% level of the free amino groups of the resin was indicated by the Kaiser ninhydrin test (5 min.). The BOC-statine-resin was then washed with methylene chloride. 2. Couplings of the Remaining Amino Acids. The peptide synthesizer was programmed to perform the following reaction cycle: (a) methylene chloride; (b) 33% trifluoroacetic acid (TFA) in methylene chloride (2 times for 5 and 25 min. each) ; (c) methylene chloride; (d) isopropyl alcohol; (e) 10% triethylamine in chloroform; and (f) ethylene chloride. The following amino acids (2.19 mmol) were then coupled successively by diisopropyl carbodiimide (4 mmol) alone or diisopropyl carbodiimide (4 mmol) plus hydroxybenzotriazole hydrate (1.47 or 0.73 mmol) and the resulting peptide-resin was washed on the synthesizer with dimethylformamide and then methylene chloride, and then cycled through the washing and deblocking steps (a) to (f) in the procedure described above. BOC-His (benzyloxycarbonyl) (coupled in the presence of 2 equivalents hydroxybenzotriazole); BOC-Gly; BOC-Val; BOC-Ala and BOC-Trp (coupled as the preformed hydroxybenzotriazole active esters made by reaction at 0°C for one hour with 1 equivalent hydroxybenzotriazole hydrate) ; BOC-Gln and pGlu (also coupled as the preformed active esters of hydroxybenzotriazole made by reaction at 0°C for one hour with 1 equivalent hydroxybenzotriazole hydrate) . The completed peptide-resin was then washed with methanol and air dried. The peptide-resin described above (1.60 g, 0.73 mmol) was mixed with anisole (2.5 ml), dithioerythreitol (50 mg) , and anhydrous hydrogen fluoride (30 ml) at 0°C. for one hour. Excess hydrogen fluoride was evaporated rapidly under a stream of dry nitrogen, and the free peptide was precipitated and washed with ether. The crude peptide was dissolved in 100 mL of 1 M acetic acid and the solution was then evaporated under reduced pressure. The crude peptide was dissolved in a minimum volume of methanol/water 1/1 and triturated with 10 volumes of ethyl acetate. The triturated peptide was applied to a column (9.4 mm I.D. x 50 cm) of octadecylsilane-silica (Whatman Partisil 10 ODS-2 M9) . The peptide was eluted with a linear gradient of 20-80% of 20/80 0.1% trifluoroacetic acid/acetonitrile in 0.1% trifluoroacetic acid in water. Fractions were examined by TLC and analytical HPLC and pooled to give maximum purity. Lyophilization of the solution from water gives 77 mg of the product as a white fluffy powder. The synthesis of the bombesin analog, D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH 2 (BIM 26187), follows. Other similar bombesin analogs were prepared by making appropriate modifications of the following synthetic method. 1) Incorporation of BOC-Leu on 4-methyl benzhydrylami-.e. 4-methyl benzhydrylamine-polystyrene resin (Bachem, Inc.) (0.72 meq/g) in the chloride ion form was placed in the reaction vessel of an ACT200 peptide synthesizer (Advanced Chem Tech, Inc.) programmed to perform the following reaction cycle: (a) methylene chloride; (b) 10% triethylamine in chloroform; (c) methylene chloride; and (d) dimethylformide. The neutralized resin was mixed with BOC-Leu and diisopropylcarbodiimide (3 molar eq. each) in methylene chloride for 1 hour. The resulting amino acid resin was washed on the synthesizer with dimethyl-formamide and treated with 5% acetic anhydride in dimethylformamide for 5 min. Then it was washed with dimethylformamide and methylene chloride. 2) Couplings of the remaining amino acids. The peptide synthesizer was programmed to perform the following reaction cycle: (a) methylene chloride; (b) 33% trifluoroacetic acid (TFA) in methylene chloride (2 times for 5 and 25 min. each) ; (c) methylene chloride; (d) isopropyl alcohol; (e) 10% triethylamine in chloroform; and (f) methylene chloride. The following amino acids (3 molar eq.) were then coupled successively by the same procedure: BOC-Leu, BOC-His (tosyl) , BOC-Gly, BOC-Val, BOC-Ala, BOC-Trp, BOC-Gln (coupled in the presence of 1 eq. hydroxybenzotriazole) , BOC-D-Phe (coupled in the presence of 1 eq. hydroxy-benzotriazole) . The completed resin was then washed with methanol and air dried. The peptide resin described above (1.41 g) was mixed with anisole (5 ml) , dithioerythreitol (50 mg) , and anhydrous hydrogen fluoride (25 ml) at 0°C for one hour. Excess hydrogen fluoride was evaporated rapidly under a stream of dry nitrogen, and the residue was washed in ether. Crude peptide was dissolved in 100 ml of 4 M acetic acid and the solution was then evaporated under reduced pressure. The crude peptide was dissolved in minimum volume of methanol/water and triturated with ethyl acetate. The triturated peptide was applied to a column (9.4 mm I.D. x 50 cm) of octadecylcilane-silica (Whatman Partisil 10 ODS - 2M9) . The peptide was eluted with a linear gradient of 20-80% of 50/50 0.1% TFA/acetonitrile in 0.1% TFA in water. Fractions were examined by analytical HPLC and appropriate fractions were evaporated to a small volume, which was further lyophilized, gives 65 mg of the product as a colorless powder. Other compounds including [D-Cpa 1 , ?-Leu 8 , desMet 9 ] Litorin, or compounds containing, e.g., ChxAla 8 or Nle 9 , were prepared as above; a statine, AHPPA, ACHPA, 0-amino acid, or γ-amino acid residue was added in the same way as was a natural «-amino acid residue, by coupling as a BOC derivative. Resins used for peptide synthesis were selected according to the chemical structure of the C-terminus of the peptide. More specifically, Merrifield resin was coupled to the first amino acid by an ester bond which, upon cleavage, yielded a carboxyl C-terminus; methylbenzhydrylamine and benzylhydrylamine resins, on the other hand, were coupled to the first amino acid by a secondary amine bond which, upon cleavage, yielded an amide C-terminus. Peptides modified at their C-terminal end were prepared by appropriate modifications of the procedure described above. For example, O-methyl ester derivatives was synthesized as described in Camble et al., "ICI 216140 A Potent .In Vivo Antagonist Analogue of Bombesin/Gastrin Releasing Peptide Derived From the C-Terminal Sequence Lacking the Final Methionine Residue", Life Science, Oct.-Nov. 1989, hereby incorporated by reference. Camble et al. describe the synthesis of an analog of bombesin having a trimethylacetyl-modified N-terminus and a methyl-ester modified C-terminus. This analog, (CH 3 ) 3 C-CO-His-Trp-Ala-Val-D-Ala-His-Leu-OCH 3 , was synthesized by solid phase methods, as described above. The N-terminal trimethylacetyl modification can be obtained by reaction of the corresponding anhydrides with the peptide. The C-terminal methyl ester modification can be obtained by treating the peptide resin with methanol and triethylamine. We describe below how a peptide analog with a substituted amide C-terminus can be prepared. Synthesis of BIM 26147 is used as an example. First, Leu-O-polystyrene Merrifield resin (1.5 g, 0.5 mmole) was placed in the reaction vessel of an Advanced ChemTech ACT 200 peptide synthesizer programmed to perform the following wash/reaction cycle (2 times for 1 and 25 min each) ; (c) methylene chloride; (d) ethanol; (e) methylene chloride; (f) 10% triethylamine in chloroform. The neutralized resin was stirred with Boc- Leu and diisopropylcarbodiimide (1.5 mmole each) in methylene chloride for 1 hr and the resulting amino acid resin was then cycled through steps (a) to (f) in the above program. The following amino acids (1.5 mmole) were then coupled successively by the same procedure: Boc-His (N- im-Boc) , Boc-Gly, Boc-Val, Boc-Ala, Boc-Trp, Boc-Gln (coupled in the presence of 1 equiv. hydroxybenzotriazole) , Boc-D-Phe (coupled in the presence of 1 equiv. hydroxybenzotriazole) . The final Boc group was then removed by 33% trifluoracetic acid treatment. After drying, the peptide resin weighed 1.9 g. The resin thus obtained (1.9 g, 0.5 mmole) was suspended in 25% propylamine/DMF and stirred (24 hr) . After removal of the volatile components, the crude peptide was dissolved in a minimum volume of 2 M acetic acid and eluted on a column (2.5 x 100 mm) of Sephadex G- 25. Fractions containing a major component by UV absorption and TLC were then pooled, evaporated to a small volume and applied to a column (1.5 x 50 cm) of Vydac octadecylsilane (10-15 uM) , followed by elution with a linear gradient of 15-45% acetonitrile in 0.1% trifluoroacetic acid in water. Fractions were examined by TLC and analytical HPLC and pooled to give maximum purity. Repeated lyophilization of the solution from water gave 220 mg of the product as a white, fluffy powder. The product was found to be homogeneous by HPLC and TLC. Amino acid analysis of an acid hydrolysate confirmed the composition of the octapeptide. The structure of the product was further confirmed by fast atom bombardment mass spectrometry. Peptides of the invention may be cyclized by formation of disulfide bridges if there are two cysteine residues present in the peptide. Effects of Bombesin Agonists/Antagonists on Acrosome Reaction I. Bombesin, GRP and ARP stimulate the spontaneous acrosome reaction The acrosome reaction, which is necessary for sperm to fertilize the egg, was induced by the following methods. For monkeys, sperm was collected, washed twice in balanced salts, resuspended in lactate/bicarbonate and dibutyryl cAMP, and then incubated for 60 minutes. These are the conditions which have been demonstrated to capacitate sperm for monkey in vitro fertilization. See Wolf, D.P. et al. Mol. Reprod. Dev. 27:261-280 (1990); Lanzendorf, S.E. et al. Mol. Reprod. Dev. 25:61-66 (1990); and Wolf D.P. et al. Biol. Reprod. 41:335-346 (1989) . All of these three publications are hereby incorporated by reference. To measure the effects of bombesin on the acrosome reaction, capacitation was conducted in the presence or absence of bombesin. After incubation, samples of sperm were removed to determine the percentage of sperm which had undergone the acrosome reaction as measured with an acrosome specific monoclonal antibody and FITC fluorescence [see Wolf, D.P. Am. J. Reprod. Immunol. 20:106-113 (1989), which is hereby incorporated by reference]. For human sperm, capacitation was achieved by overnight incubation of sperm in balanced salt and 0.3% bovine serum albumin, after which bombesin was added to induce the acrosome reaction. As shown in Fig. 5, concentrations as low as 5 nM bombesin caused a 2-fold increase in the acrosome reaction in both monkey and human sperm. The bo besin- induced stimulation of the acrosome reaction could be blocked by a bombesin antagonist BIM 26147 (See Fig. 6) . High doses of progesterone (1 μg/ml) acting through an as yet unknown mechanism also induce the acrosome reaction. Thomas, P. et al. Influx. Biochem. J. 264:539-546 (1989); Black ore, P.F., et al. J. Biol. Chem. 265:1376-1380 (1990). As also shown in Fig. 6, the progesterone induced acrosome reaction could also be blocked by BIM 26147. Human GRP, like bombesin, was also found to be a potent peptide capable of stimulating the acrosome reaction, i.e., it is active at 1 nM. The GRP-induced stimulation of the acrosome reaction could be blocked by a bombesin antagonist BIM-26028 (data not shown; for structure, see infra) . Similarly, monkey ARP-22 was found to be as potent as bombesin in stimulating the acrosome reaction. II. Effect of Various Bombesin Analogs on the Acrosome Reaction Eight bombesin analogs, BIM 26136, BIM 26187, BIM 26189, BIM 26224, BIM 26226, BIM 26244, and BIM 26028, were used to test their effect on the acrosome reaction, either alone or in the presence GRP, in a manner described above. The structures of the analogs tested are as follows: BIM 26136: H-D-Nal-Gln-Trp-Ala-Val-Gly-His-Leu-ψ(CH 2 - NH)-Phe-NH 2 BIM 26187: H-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH 2 BIM 26189: H-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-Cpa-NH 2 BIM 26224: H-D-Phe-Gln-Trp-Ala-Val-Gly-His-Phe-Nle-NH 2 BIM 26226: H-D-F 5 -Phe-Gln-Trp-Ala-Val-D-Ala-His-Leu-OCH 3 BIM 26244: H-Propionyl-His-Trp-Ala-Val-D-Ala-His-Leu- OCH 3 BIM 26028: H-pGlu-Gln-Arg~Leu-Gly-Asn-Gln-Trp-Ala-Val- Gly-His-Leu-ψ(CH 2 -NH)-Leu-NH 2 (SEQ ID NO: 24) TABLE 1 EFFECT OF VARIOUS ANALOGS ON THE ACROSOME REACTION IN THE PRESENCE OR ABSENCE OF GRP (% Acrosome Reacted) * Final concentration: 50 nM # Final concentration: 2 nM As shown in Table 1 above, among the seven analogs tested, BIM 26136 is the most potent in inducing the acrosome reaction. III. Bombesin analog BIM 26147 blocks the in vitro fertilization of the monkey egg by monkey sperm. As discussed above, while bombesin and some analogs thereof stimulate the acrosome reaction, other bombesin analogs block the acrosome reaction which is induced either by bombesin or by natural products such as progesterone. For example, BIM 26147 completely blocks progesterone and bombesin induced stimulation of the acrosome reaction. Since the acrosome reaction is necessary for successful fertilization, we predicted that some bombesin analogs should be able to block fertilization. The prediction was confirmed by blocking in vitro fertilization of rhesus monkey ova by sperm by adding BIM 26147 to the fertilization reaction. More specifically, the standard in vitro fertilization protocol was followed [see Wolf, D.P. et al. Mol. Reprod. Dev. 27:261-280 (1990) and Lanzendorf, S.E. et al. Mol. Reprod. Dev. 25:61-66 (1990), hereby incorporated by reference] , with the exception that 100 nM BIM 26147 was added to the capacitation and fertilization reactions for some of the eggs. Two independent experiments were conducted. In the first experiment, 1 of 5 BIM 26147-treated eggs were fertilized versus 3 of 6 control eggs; in the second experiment, 0 of 4 BIM 26147-treated eggs were fertilized versus 12 of 20 control eggs. The methods set forth above are well-known in the art. Thus, it is within the ability of a skilled artisan to use such methods in screening compounds for bombesin analogs capable of promoting and blocking fertilization, respectively. OTHER EMBODIMENTS The term "ARP" includes any bombesin agonists which are substantially homologous (i.e., 60% or greater) to human and rhesus monkey ARP's identified above as SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, as well as any naturally occurring peptide in other species which corresponds to one of the above-identified ARP's. Homologous refers to the sequence similarity between two peptides. When a position in both of the two compared sequences is occupied by the same amino acid monomeric subunit. The homology between two sequences is a function of the number of matching or homologous positions shared by the two sequences. For example, 6 of 10 of the positions in two sequences are matched or homologous then the two sequences are 60% homologous. Other ARP's which are also included in this invention are allelic variations, natural mutants, induced mutants, peptides encoded by DNA that hybridizes under high or low stringency conditions (see below) to SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12, and peptides specifically bound by antisera to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6. The invention also includes a pure DNA characterized as including a sequence which hybridizes under highly stringent conditions (e.g., as described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1989) to a nucleic acid probe which includes at least a six-nucleotide segment (preferably at least 10 nucleotides) of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12. Alternatively, the DNA of the invention may be characterized as being capable of hybridizing under low- stringency conditions to a nucleic acid probe which includes the coding sequence of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12. An example of such low-stringency conditions is as follows: prehybridization in 50% forma ide, 5X SSC, 25 mM potassium phosphate buffer (pH 7.4), 5X Denhardt's, and 50 μg/ml denatured salmon sperm DNA for 4-12 hours at 20°C; hybridization for 12-24 hours at 20°C; and washing in 5X SSC containing 0.1% SDS, at 20°C. The invention also includes any biologically active analog of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6. By "biologically active analog" is meant any compound which possesses an acrosome reaction-promoting activity similar to or greater than that exhibited by bombesin as shown in Fig. 5. Most preferably, it possesses at least 75% of the activity of bombesin. Analogs can differ from naturally occurring ARP's in amino acid sequence or can be modified in ways thac do not involve sequence, or both. Alterations in primary sequence include genetic variants, both natural and induced. Also included are analogs that include residues other than naturally occurring L-amino acids. The existence of the above-described active ARP's does not rule out the existence of other active bombesin- like peptides in the male and female reproductive tract, including GRP, NMB and potentially other not yet characterized bombesin-like peptides. Other embodiments are also within the following claims. SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: Spindel, Eliot R. Vijayaraghavan, Srinivasan Nagalla, Srinivasa R. Li, Kang (ii) TITLE OF INVENTION: DNA SEQUENCE WHICH ENCODES A PEPTIDE CAPABLE OF PROMOTING ACROMSOME REACTION (iii) NUMBER OF SEQUENCES: 19 (Iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: Fish & Richardson (B) STREET: 225 Franklin Street (C) CITY: Boston (D) STATE: Massachusetts (E) COUNTRY: U.S.A. (F) ZIP: 02110-2804 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: 3.5" Diskette, 1.44 Mb (B) COMPUTER: IBM PS/2 Model 50Z or 55SX (C) OPERATING SYSTEM: MS-DOS (Version 5.0) (D) SOFTWARE: WordPerfect (Version 5.1) (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: 07/919,731 (B) FILING DATE: 27 July 1992 (C) CLASSIFICATION: (vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: (B) FILING DATE: (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Clark, Paul T. (B) REGISTRATION NUMBER: 30,162 (C) REFERENCE/DOCKET NUMBER: 00537/068002 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: (617) 542-5070 (B) TELEFAX: (617) 542-8906 (C) TELEX: 200154 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 27 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A ( ix ) FEATURE : (D) OTHER INFORMATION: The sequence has an amide C-terminus (i.e., CO'NH-,), rather than a carboxyl C-terminus (i.e., CO-OH) . (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1: Met Leu Val Lys Arg Ala Arg Cys Leu Leu Ser Cys His Ala Ser Gly 1 5 10 15 Gin Gly Cys Leu Gly lie Pro Gly His Leu Met 20 25 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A (ix) FEATURE: (D) OTHER INFORMATION: The sequence has an amide C-terminus (i.e., CO«NH 2 ), rather than a carboxyl C-terminus (i.e., CO-OH). (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2: Ala Arg Cys Leu Leu Ser Cys His Ala Ser Gly Gin Gly Cys Leu Gly 1 5 10 15 He Pro Gly His Leu Met 20 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A (ix) FEATURE: (D) OTHER INFORMATION: The sequence has an amide C-terminus (i.e., CO-NH j ), rather than a carboxyl C-terminus (i.e., CO-OH). (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3: Gin Gly Cys Leu Gly He Pro Gly His Leu Met 1 5 10 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 27 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A ( ix ) FEATURE : (D) OTHER INFORMATION: The sequence has an amide C-terminus (i.e., CO'NH ), rather than a carboxyl C-terminus (i.e., CO-OH). (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4: Met Leu Val Lys Arg Ala Ser Tyr Leu Leu Ser Cys His Thr Ser Gly 1 5 10 15 Gin Ser Cys Leu Gly He Pro Gly His Leu Met 20 25 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A (ix) FEATURE: (D) OTHER INFORMATION: The sequence has an amide C-terminus (i.e., CO«NH 2 ), rather than a carboxyl C-terminus (i.e., CO-OH) . (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5: Ala Ser Tyr Leu Leu Ser Cys His Thr Ser Gly Gin Ser Cys Leu Gly 1 5 10 15 He Pro Gly His Leu Met 20 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A (ix) FEATURE: (D) OTHER INFORMATION: The sequence has an amide C-terminus (i.e., CO«NH 2 ), rather than a carboxyl C-terminus (i.e., CO-OH). (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 6: Gin Ser Cys Leu Gly He Pro Gly His Leu Met 1 5 10 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 84 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7: ATGCTTGTGA AAAGGGCCAG GTGTCTTCTG TCTTGCCATG CAAGTGGGCA GGGCTGCTTG GGAATACCAG GGCACTTAAT GGGG (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 69 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8: GCCAGGTGTC TTCTGTCTTG CCATGCAAGT GGGCAGGGCT GCTTGGGAAT ACCAGGGCAC TTAATGGGG (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 36 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9: CAGGGCTGCT TGGGAATACC AGGGCACTTA ATGGGG (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 84 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10: ATGCTTGTGA AAAGGGCCAG CTATCTTCTG TCTTGCCATA CAAGTGGGCA GAGCTGCCTG GGAATACCAG GGCACTTAAT GGGG (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 69 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11: GCCAGCTATC TTCTGTCTTG CCATACAAGT GGGCAGAGCT GCCTGGGAAT ACCAGGGCAC TTAATGGGG (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 46 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12: CAGAGCTGCC TGGGAATACC AGGGCACTTA ATGGGG (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 645 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13: GGCAACTCTA GAGGGGTGTG TATGTGGCAG TTCAGGGACA GTTTGAGCTT TCGGGTAGAG GCAGCCTAGG GAAACCGGCA TAAAGCAGTT TCTTTCTCTA TTCCATGGAA GCTGC ATG CTT GTG AAA AGG GCC AGG TGT CTT CTG TCT TGC CAT GCA AGT GGG Met Leu Val Lys Arg Ala Arg Cys Leu Leu Ser Cys His Ala Ser Gly CAG GGC TGC TTG GGA ATA CCA GGG CAC TTA ATG GGG AAA AAG AGC ACA Gin Gly Cys Leu Gly He Pro Gly His Leu Met Gly Lys Lys Ser Thr GGG GAG TCT TCT GTT TCT GAG AGA GGG AGC CTA AAG CAG CAG CTG AGA Gly Glu Ser Ser Val Ser Glu Arg Gly Ser Leu Lys Gin Gin Leu Arg GAG TAC ATC AGG TGG GAA GAA GCT GCA AGC AAT TTG CTG GGT CTC ATA Glu Tyr He Arg Trp Glu Glu Ala Ala Ser Asn Leu Leu Gly Leu He GAA GCA AAG GAG AAC AGA AAC CAC CAG CCA CCT CAA CCC AAG GCC CTG Glu Ala Lys Glu Asn Arg Asn His Gin Pro Pro Gin Pro Lys Ala Leu GGC AAT CAG CAG CCT TCG TGG GAT TCA GAG GAT AGC AGC AAC TTC AAA Gly Asn Gin Gin Pro Ser Trp Asp Ser Glu Asp Ser Ser Asn Phe Lys GAT GTA GGT TCA AAA GGC AAA GTT GGT AGA CTC TCT GCT CCA GGT TCT Asp Val Gly Ser Lys Gly Lys Val Gly Arg Leu Ser Ala Pro Gly Ser CAA CGT GAA GGA AGG AAC CCC CCA GCT GAA CCA GCA ATG ACA ATG ATG Gin Arg Glu Gly Arg Asn Pro Pro Ala Glu Pro Ala Met Thr Met Ala GCC TCT CTC AAA GGA GAA AAA CAA AAC CCG TAA GAGACTGCGT TCTGCAAGCA Ala Ser Leu Lys Gly Glu Lys Gin Asn Pro TCAGTTCTAC GGATCATCAA CAAGATTTCC TTGTGCAAAA TATTTGACTA TTCTTGTATC TTTCATCCTT GACTAAATTC GTGATTTTCA AGC (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 787 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14: AGCAACTCTA GAGGGGTGTG TATGTGGCAG TTTAGGGACA GTTTGAGCTT TCAGGTAGAG GCAGCCTAGG GAAACTGGCA TAAAGCAGTT TCTTTCTCTA TTCCATGGAA GTTGC ATG CTT GTG AAA AGG GCC AGC TAT CTT CTG TCT TGC CAT ACA AGT GGG Met Leu Val Lys Arg Ala Ser Tyr Leu Leu Ser Cys His Thr Ser Gly CAG AGC TGC CTG GGA ATA CCA GGG CAC TTA ATG GGG AAA AAG AGC ACA Gin Ser Cys Leu Gly He Pro Gly His Leu Met Gly Lys Lys Ser Thr GGG GAG TCT TCT TCT GTT TCT GAG AGA GGG AGC CTG AAG CAG CAG CTG Gly Glu Ser Ser Ser Val Ser Glu Arg Gly Ser Leu Lys Gin Gin Leu AGA GAG TAC ATC AGG TGG GAA GAA GCT GCA AGG AAT TTG CTG GGT CTC Arg Glu Tyr He Arg Trp Glu Glu Ala Ala Arg Asn Leu Leu Gly Leu ATA GAA GCA AAG GAG AAC AGA AAC CAC CAG CCA CCT CAA CCC AAG GCC He Glu Ala Lys Glu Asn Arg Asn His Gin Pro Pro Gin Pro Lys Ala TTG GGC AAT CAG CAG CCT TCG TGG GAT TCA GAG GAT AGC AGC AAC TTC Leu Gly Asn Gin Gin Pro Ser Trp Asp Ser Glu Asp Ser Ser Asn Phe AAA GAT GTA GGT TCA AAA GGC AAA GTT GGT AGA CTC TCT GCT CCA GGT Lys Asp Val Gly Ser Lys Gly Lys Val Gly Arg Leu Ser Ala Pro Gly TCT CAA CGT GAA GGA AGG AAC CCC CAG CTG AAC CAG CAA TGA Ser Gin Arg Glu Gly Arg Asn Pro Gin Leu Asn Gin Gin TAATGATGGC CTCTCTCAAA AGAGAAAAAC AAAACCCCTA AGAGACTGAG TTCTGCAAGC ATCAGTTCTA CGGATCATCA ACAAGATTTC CTTGTGCAAA ATATTTGACT ATTCTGTATC TTTCATCCTT GACTAAATTC GTGATTTTCA AGCAGCATCT TCTGGTTTAA ACTTGTTTGC TGTGAACAAT TGTCGAAAAG AGTCTTCCAA TTAATGCTTT TTTATATCTA GGCTACCTGT TGGTTAGATT CAAGGCCCCC GAGCTGTTAC CATTCACAAT AAAAGCTTAA ACAC (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15: GTAGACTCTC TGCTCCAG (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16: AAACCAGAAG ATGCTGCT (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 17: (i) SEQUENCE CHARACTERISTICS: (λ) LENGTH: 21 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17: GTGTATGTGG CAGTTCAGGG A (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 16 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18: ATGGCAAGAC AGAAGA (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 17 (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19: TGCATGCTTG TGAAAAG SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: Spindel, Eliot R. Nagalla, Srinivasa R. Vijayaraghavan, Srinivasan Archibond, Anthony (ii) TITLE OF INVENTION: METHOD OF CONTROLLING FERTILIZATION (iii) NUMBER OF SEQUENCES: 5 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: Fish & Richardson (B) STREET: 225 Franklin Street (C) CITY: Boston (D) STATE: Massachusetts (E) COUNTRY: U.S.A. (F) ZIP: 02110-2804 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: 3.5" Diskette, 1.44 Mb (B) COMPUTER: IBM PS/2 Model 50Z or 55SX (C) OPERATING SYSTEM: MS-DOS (Version 5.0) (D) SOFTWARE: WordPerfect (Version 5.1) (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: 07/919,731 (B) FILING DATE: 07/27/92 (C) CLASSIFICATION: (vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: (B) FILING DATE: (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Clark, Paul T. and Tsao, Y. Rocky (B) REGISTRATION NUMBER: 30,162 and 34,053 (C) REFERENCE/DOCKET NUMBER: 00537/068001 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: (617) 542-5070 (B) TELEFAX: (617) 542-8906 (C) TELEX: 200154 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 14 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A (ix) FEATURE: (D) OTHER INFORMATION: The sequence contains at position 1 a pyroglutamate, rather than a glutamate, and has an amide C- terminus (i.e., CO«NH 2 ), rather than a carboxyl C-terminus (i.e., CO»OH) . (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20: Glu Gin Arg Leu Gly Asn Gin Trp Ala Val Gly His Leu Met 5 10 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 27 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A (ix) FEATURE: (D) OTHER INFORMATION: The sequence has an amide C-terminus (i.e., CO-NH 2 ), rather than a carboxyl C-terminus (i.e., CO-OH). (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21: Ala Pro Val Ser Val Gly Gly Gly Thr Val Leu Ala Lys Met Tyr Pro 5 10 15 Arg Gly Asn His Trp Ala Val Gly His Leu Met 20 25 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A (ix) FEATURE: (D) OTHER INFORMATION: The sequence contains at position 1 a pyroglutamate, rather than a glutamate, has a reduced peptide bond (i.e., CH-,»NH instead of CO«NH) between Leu and Leu, and has an amide C-terminus (i.e., CO«NH 2 ), rather than a carboxyl C-terminus (i.e., CO'OH). (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22: Glu Gin Trp Ala Val Gly His Leu Leu 5 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A (ix) FEATURE: (D) OTHER INFORMATION: The sequence contains at position 1 a pyroglutamate, rather than a glutamate, has a reduced peptide bond (i.e., CH-.«NH instead of CO*NH) between Phe and Leu, and has an amide C-terminus (i.e., CO«NH 2 ), rather than a carboxyl C-terminus (i.e., CO-OH). (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23: Glu Gin Trp Ala Val Gly His Phe Leu 5 (2) INFORMATION FOR SEQUENCE IDENTIFICATION NUMBER: 24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 14 (B) TYPE: amino acid (C) STRANDEDNESS: N/A (D) TOPOLOGY: N/A (ix) FEATURE: (D) OTHER INFORMATION: The sequence contains at position 1 a pyroglutamate, rather than a glutamate, has a reduced peptide bond (i.e., CH-.-NH instead of CO«NH) between Leu and Leu, and has an amide C-terminus (i.e., CO«NH 2 ), rather than a carboxyl C-terminus (i.e., CO-OH). (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24: Glu Gin Arg Leu Gly Asn Gin Trp Ala Val Gly His Leu Leu 5 10

Claims: What is claimed is: CLAIMS 1. A pure DNA encoding a peptide selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6. 2. The DNA of claim 1, wherein said peptide is SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, or SEQ ID NO: 6. 3. The DNA of claim 2, wherein said peptide is SEQ ID NO: 3, or SEQ ID NO: 6. 4. The DNA of claim 1 consisting essentially of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12. 5. The DNA of claim 4 consisting essentially of SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 12. 6. The DNA of claim 5 consisting essentially of SEQ ID NO: 9, or SEQ ID NO: 12. 7. A vector containing the DNA of claim 1 or 4. 8. A cell containing the DNA of claim 1 or 4. 9. The cell of claim 8, wherein said DNA is introduced into said cell in a manner allowing said cell to express said peptide. 10. A pure peptide selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6. 11. The peptide of claim 10 is SEQ ID NO: 2; SEQ ID NO: 3, SEQ ID NO: 5, or SEQ ID NO: 6. 12. The peptide of claim 10, wherein said peptide is SEQ ID NO: 3, or SEQ ID NO: 6. 13. A pharmaceutical composition comprising the peptide of claim 10, 11 or 12 and a pharmaceutically acceptable carrier. 14. A method of promoting fertilization by stimulating the arosome reaction, said method comprising the step of contacting sperm either at the time of sperm capacitation or at the time of egg fertilization with an effective amount of bombesin agonist. 15. The method of claim 14 as applied to in vitro fertilization or artificial insemination for promoting fertilization. 16. The method of claim 14 in which said bombesin or its agonist is administered vaginally to a female subject for promoting fertilization. 17. The method of claim 14 in which said bombesin or its agonist is administered systemically or locally to a male subject for promoting fertilization. 18. The method of claim 17 in which said bombesin or its agonist is administered locally. 19. The method of claim 18 in which said bombesin or its agonist is administered by implantation of a biodegradable or retrievable polymer formulation in the scrotum. 20. The method of claim 14, 15, 16 or 17 in which said bombesin or its agonist is bombesin, GRP or ARP. 21. A method of blocking fertilization by inhibiting the arosome reaction, said method comprising the step of contacting sperm either at the time of sperm capacitation or at the time of egg fertilization with an effective amount of bombesin antagonist. 22. The method of claim 21 in which said bombesin antagonist is administered vaginally to a female subject for blocking fertilization. 23. The method of claim 22 in which said bombesin antagonist is administered in a formulation consisting of sponge, foam, jelly, and a biocompatible matrix. 24. The method of claim 21 in which said bombesin antagonist is administered systemically or locally to a male subject for blocking fertilization. 25. The method of claim 24 in which said bombesin antagonist is administered locally. 26. The method of claim 25 in which said bombesin antagonist is administered by implantation of a biodegradable or retrievable polymer formulation in the scrotum.

Inventors: LI KANG, NAGALIA SRINIVASA R, SPINDEL ELIOT R, VIJAYARAGHAVAN SRINIVASAN, LI, KANG, NAGALIA, SRINIVASA, R., SPINDEL, ELIOT, R., VIJAYARAGHAVAN, SRINIVASAN
Applicants: OREGON MEDICAL RES FOUND
Application year: 1993
Main classification: A01N37
IPC codes: A61K38, A61P13, A61P15, C07K7, C07K14, C12N15