BIOLOGICALLY ACTIVE AMPHIPHILIC PEPTIDES AND METHOD OF INHIBITING GROWTH OF TARGET CELLS, VIRUS OR VIRALLY-INFECTED CELL

Abstract: A biologically active amphiphilic peptide which in accordance with an aspect of the present invention, includes one of the following basic structures X1 through X7, wherein: X1 is -[R1-R2-R2-R3-R1-R2-R2]-n; X2 is -[R2-R2-R3-R1-R2-R2-R1]-n; X3 is -[R2-R3-R1-R2-R2-R1-R2]-n; X4 is -[R3-R1-R2-R2-R1-R2-R2]-n; X5 is-[R1-R2-R2-R1-R2-R2-R3]-n; X6 is -[R2-R2-R1-R2-R2-R3-R1]-n; and X7 is-[R2-R1-R2-R2-R3-R1-R2]-n; wherein R1 is a basic hydrophilic amino acid, R2 is a hydrophobic amino acid, R3 is a neutral hydrophilic, basic hydrophilic or hydrophobic amino acid and n is from 2 to 5. The peptide compositions are used to inhibit growth of a target cell, virus or virally-infected cell.

Description: BIOLOGICALLY ACTIVE AMPHIPHILIC PEPTIDES AND METHOD OF INHIBITING GROWTH OF TARGET CELLS, VIRUS OR VIRALLY-INFECTED CELL This application is a continuation-in-part of application Serial No. 476,629, filed February 8, 1990. This invention relates to biologically active peptides, an d more particularly to novel biologically active peptides and uses therefor. In accordance with an aspect of the present invention, there is provided a biologically active amphiphilic peptide which includes one of the following basic structures X. through X_ wherein: X ] is -[ R l "R 2 "R 2 "R 3 "R l "R 2 "R 2 ]" n X. is - lR 2- R r R 2- R l ] -n is -< R 2- R 2- R r R 2- R 2- R 3- R l ] -n and X- is -lR 2 - R l "R 2 "R 2 "R 3 "R l "R 2 ]" n wherein R. is a basic hydrophilic amino acid, R- is a hydrophobic amino acid, R_ is a neutral hydrophilic or hydrophobic amino acid, and n is from 2 to 5. The basic hydrophilic amino acids include, but are not limited to Lys, Arg, His, Orn, homoarginine (Har), 2, 4-diamino butyric acid (Dbu), and p-aminophenylalanine. The hydrophobic amino acids include, but are not limited to Ala, Cys, Phe, Gly, lie, Leu, Met, Pro, Val, Trp, Tyr, norleucine (Nle), norvaline (Nva), and cyclohexylalanine (Cha). The neutral hydrophilic amino acids include, but are not limited to Asn, Gin, Ser and Thr. In accordance with one embodiment, when the peptide includes the structure X.., the peptide may include the following s as hereinabove described, and Y is: or (vi) R 2 -R 2 -R_-R--R 2 -R 2 , wherein R., R 2 , and R- are as hereinabove described In accordance with another embodiment, when the peptide includes the structure X., the peptide may include the following structure: X 1 -Z 1 , wherein X. is as hereinabove described, and Z., is: (i) R χ ; (ii) R 1 -R 2 ; (iii) R 1 -R 2 -R 2 ; (iv) R 1 -R 2 -R 2 -R 3 ; (v) R 1 -R 2 -R 2 -R 3 -R 1 ; or (vi) R 1 -R 2 -R 2 -R 3 -R 1 -R 2 . In accordance with yet another embodiment, the peptide may include the following structure: (Y.) -X.-fZ.-). , wherein Y λ and ∑ 1 are as previously defined, a is 0 or 1, and b is 0 or 1. When the peptide includes the structure X 2 , the peptide may include the following structure: Y„ - X„, wherein X„ is as hereinabove described, and Y, is: 2 2 4 *• (i) R χ ; (ii) * 2 - R ι> m (iii) R 2 - 2 -R ι; (iv) R 1 -R 2 -R 2 - 1 ; (v) R 3 -R 1 -R 2 -R 2 -R 1 ; or (vi) R 2 - 3 -R R 2 -R 2 -R In another embodiment, the peptide may include the followin g structure: X 2 - Z 2 wherein X 2 is as hereinabove described, and Z is: (i) R 2 ; (ii) R 2 -R 2 ; (iii) R 2 -R 2 -R 3 ; (iv) R 2 -R 2 -R 3 -R ι; (V) R 2 -R 2 - 3 -R 1 -R 2 ; or (Vi) R 2 -R 2 -R 3 -R 1 -R 2 -R 2 . In accordance with yet another embodiment, the peptide may include the following structure: ^ Y 2*a " X 2 " ^ Z 2*b' whβrein γ 2 and Z 2 arβ as P rβviousl y defined, a is 0 or 1, and b is 0 or 1. In accordance with another embodiment, when the peptide includes the structure X 3 , the peptide may include the following structure: Y_ - X 3 wherein X 3 is as hereinabove described, and Y_ is: (i) R 2 ; (ii) R-^ j , (iii) R 2 -R 1 -R 2 ; (iv) R 2 -R 2 -R 1 -R 2 ; (v) R 1 -R 2 -R 2 -R 1 -R 2 ; or (vi) R 3 -R 1 -R 2 -R 2 -R 1 -R 2 , wherein R^ R 2 , and R 3 are as hereinabove described. In accordance with another embodiment, when the peptide includes the structure 3 , the peptide may include the following structure: X 3 - Z 3 wherein X 3 is as ^ hereinabove described, and Z 3 is: (i) R 2 ; (ii) R 2 -R 3 (iii) R 2 -R 3 -R ι; (iv) R 2 -R 3 -R 1 -R 2 ; (v) R 2 -R 3 -R 1 -R 2 -R 2 ; or (vi) R 2 -R 3 -R 1 -R 2 -R 2 -R 1 . In accordance with yet another embodiment, the peptide may include the following structure: (Y 3 ) a - X 3 - (2 3 ) b , wherein Y and Z are as previously defined, a is 0 or 1, and b is 0 or 1. In accordance with yet another embodiment, when the peptide includes the structure X 4 , the peptide may include the following structure: 4 - X., wherein X 4 is as hereinabove described, and Y. is: (i) R 2 ; (ii) R 2 -R 2 ; (iii) R 1 -R 2 -R 2 ; (iv) R 2 -R 1 -R 2 -R 2 ; (v) R 2 -R 2 -R 1 -R 2 -R 2 ; or (vi) R.-R 2 -R 2 -R,-R 2 -R 2 , wherein R-, R 2 and R 3 are as hereinabove described. In accordance with another embodiment, when the peptide includes the structure X 4 , the peptide may include the following is as hereinabove described, and Z 4 is: (v) R 3 -R 1 -R 2 -R 2 -R 1 or ( i) R 3 -R 1 -R 2 -R 2 -R 1 -R 2 . In accordance with yet another embodiment, the peptide may include the following structure: ( v 4> a " x (Z 4>b' whβrβin x 4 an <* Z 4 are as previously defined, a is 0 or 1, and b is 0 or 1. In accordance with a further embodiment, when the peptide includes the structure X 5 , the peptide may include the following structure: Y.-Xς, wherein X- is as hereinabove described, and Y is : (i) R 3 ; (ii) R 2 -R 3 ; (iii) R 2 -R 2 -R 3 ; (iv) R R 2 -R 2 -R 3 ; (V) R 2 -R 1 -R 2 -R 2 -R 3 ; or (vi) R 2 -R 2 -R 1 -R 2 -R 2 -R 3 , wherein R., R 2 , and R 3 are as hereinabove described. In accordance with another embodiment, when the peptide includes structure X_, the peptide may include the following structure: X-. - Z g wherein X- is as hereinabove described, and Z- is: (i) R n ; (ii) R 1 -R 2 ; (iii) R 1 -R 2 -R 2 ; (iv) R 1 - 2 -R 2 -R 1 ; (V) R 1 -R 2 -R 2 -R 1 -R 2 ; or (Vi) R 1 -R 2 -R 2 -R 1 -R 2 -R 2 . In accordance with yet another embodiment, the peptide may include the following structure: (Y_) - X- (Z-) b wherein X 5 and Z 5 are as previously defined, a is 0 or 1, and b is 0 or 1. In accordance with a further embodiment, when the peptide includes the structure X g , the peptide may include the following structure: Y6- - X6, wherein X Λ o is as hereinabove described, and Y ft σ is: (ϋi) R 2 "R 3 "R 1 ; ( iv) 2 - 2 -R 3 - ι ; (V) R 1 -R 2 -R 2 -R 3 -R 1 ; or (vi) R 2 -R 1 -R 2 -R 2 -R 3 -R 1 , wherein R 1 , R , and R 3 are as hereinabove described. In accordance with another embodiment, when the pepti d e includes the structure X g , the peptide may include the following is (V) R 2 .R 2 -R 1 -R 2 -R 2 ; or (Vi) R 2 -R 2 -R 1 -R 2 -R 2 -R 3 . In accordance with yet another embodiment, the peptide may include the following structure: (Y g ) a - Xg ( Z 5)*b' wherein Y g and Z g are as previously defined, a is 0 or 1, and b is 0 or 1. In accordance with one embodiment, when the peptide includes the structure X_, the peptide may include the structure Y--X-, wherein X_ is as hereinabove described, and Y_ is: (i) R 2 ; (ii) R χ -R 2 ; (iv) R 2 -R 3 -R 1 -R 2 ; (v) R 2 -R 2 -R 3 -R 1 -R 2 ; or (vi) wherein R., R 2 , and R 3 are as hereinabove described. In accordance with a further embodiment, when the peptide includes the structure X_, the peptide may include the following structure: X- - Z η wherein X- is as hereinabove described, and Z η is: (i) R 2 ; (ii) R 2 -R ι; (iv) R 2 "R l "R 2 "R 2' (v) R 2 -R 1 -R 2 -R 2 -R 3 ; or (vi) R 2 -R 1 -R 2 -R 2 -R 3 -R 1 . In accordance with yet another embodiment, the peptide may include the following structure: (Y 7 ) a - Xy (Z_) b , wherein Y_ and Z-, are as previously defined, a is 0 or 1, and b is 0 or 1. The peptides and/or analogues or derivatives thereof, may b e C-terminal acids or amides. In a preferred embodiment, n is 3, and most preferably the peptide is of one of the following structures listed below and also listed in the accompanying sequence listing: (Lys lie Ala Gly Lys lie Al (Lys lie Ala Lys lie Ala Gly (Lys He Ala Gly Lys lie Gly (Lys Leu Ala Gly Lys Leu ^la (Lys Phe Ala Gly Lys Phe Ala (Lys Ala Leu Ser Lys Ala Leu (Lys Leu Leu Lys Ala Leu Gly (Lys Ala He Gly Lys Ala He (Gly He Ala Lys He Ala Lys (Lys He Ala Lys He Phe Gly (Gly He Ala Arg He Ala Lys (Lys Phe Ala Arg He Ala Gly (Gly Phe Ala Lys He Ala Lys (Lys He Ala Gly Orn He Ala (Lys He Ala Arg He Ala Gl (Orn He Ala Gly Lys He Al (Gly He Ala Arg He Phe Lys (Lys Nle Ala Gly Lys Nle Al (Lys Nle Ala Gly Lys He Al (Lys He Ala Gly Lys Nle Al (Lys Nva Ala Gly Lys Nva Al (Lys Nva Ala Gly Lys He Al (Lys Leu Leu Ser Lys Leu Gl (Lys Leu Leu Ser Lys Phe Gl (Lys He Ala Gly Lys Nva Ala (His He Ala Gly His He Ala (Ala Gly Lys He Ala Lys He (He Ala Lys He Ala Gly Lys (Lys He Ala Gly Arg He Ala (Arg He Ala Gly Arg ' lie Ala (Lys Val Ala Gly Lys He Ala (Lys He Ala Gly Lys Val Ala (Ala Lys He Ala Gly Lys He (Orn He Ala Gly Orn He Ala (Lys Phe Ala Gly Lys He Ala (Lys He Ala Gly Lys Phe Ala (Lys Cha Ala Gly Lys He Ala (Lys Nle Ala Lys He Ala Gly (Arg He Ala Gly Lys He Ala (Har He Ala Gly Har He Ala (Xaa He Ala Gly Lys He Ala (Lys He Ala Gly Xaa He Ala In (SEQ ID NO:41) and (SEQ ID NO-.42), Xaa is p-aminophenylalanine. In accordance with another aspect of the present invention, there is provided a biologically active amphiphilic peptide which includes the following basic structure X 14 : R l" R 2" R 2" R 3" 4 'R 2 "R 2 "R l "R 2 "R 2 "R 2 "R 4 "R 2 "R 2' wherein R., R 2 , and R 3 are as hereinabove described, and R 4 is a basic hydrophilic or hydrophobic amino acid. In accordance with one embodiment, the peptide may include the following structure: Y 14" X 14' whβrein x i is as hereinabove described, and Y 14 S: (i) R 2 ; (ii) R 2 -R 2 ; (iii) R 4 -R 2 - 2 ; (iv) R 3 -R 4 - 2 -R 2 ; (v) R 2 -R 3 - 4 -R 2 -R 2 ; (vi) R 2 -R 2 -R 3 -R 4 -R 2 -R 2 , or (vii) R R 2 -R 2 -R 3 - 4 -R 2 -R 2 ,wherein R χ , R 2 , R 3 and R 4 are as hereinabove described. In accordance with another embodiment, the peptide may include the following structure: 4 is as hereinabove described and Z.. is: (V) R R 2 -R 2 - 3 -R 4 ; (vi) R 1 -R 2 -R 2 -R 3 -R 4 -R 2 ; or (vii) R 1 -R 2 -R 2 -R 3 -R 4 -R 2 -R 2 , wherein R χ , R 2 , R 3 , and R 4 are as hereinabove described. In accordance with yet another embodiment the peptide may include the following structure: (Y. 4 ) - 14 -(Z 14 ). , wherein X and Y are as previously defined, a is 0 or 1, and b is 0 or 1. In a preferred embodiment, the peptide has the following structural formula as indicated in the accompanying sequence listing: (SEQ ID NO: 43)-NH 2 . In another preferred embodiment, the peptide has the following structural formula as indicated in the accompanying sequence listing: (SEQ ID NO: 44)-NH 2 . In accordance with a further embodiment, the peptide has one of the following structural formulae as indicated in the accompanying sequence listing: (SEQ ID NO: 45)-NH 2 _ ιo _ (SEQ ID NO: 46)-NH 2 (SEQ ID NO: 47)-NH 2 (SEQ ID NO: 48)-NH 2 (SEQ ID NO: 49)-NH 2 (SEQ ID NO: 50)-NH 2 (SEQ ID NO: 51)-NH 2 (SEQ ID NO: 52)-NH 2 (SEQ ID NO: 53)-NH 2 (SEQ ID NO: 54)-NH 2 (SEQ ID NO: 55)-NH 2 (SEQ ID NO: 56)-NH 2 (SEQ ID NO: 57)-NH 2 (SEQ ID NO: 58)-NH 2 (SEQ ID NO: 59)-NH 2 In accordance with another aspect of the present invention, there is provided a biologically active amphiphilic peptide which includes the following structural formula: -(Lys He Ala Lys Lys He Ala)- wherein n is from 2 to 5. Preferably, n is ' 3, and the peptide has the following structural formula: (Lys He Ala Lys Lys He Ala) 3 -NH 2 . (SEQ ID NO:60). In accordance with another aspect of the present invention, there is provided a biologically active amphiphilic peptide selected from the group consisting of the following structural formulae as given in the accompanying sequence listing: (SEQ ID NO: 61)-NH 2 (SEQ ID NO: 62)-NH 2 (SEQ ID NO: 63)-NH 2 (SEQ ID NO: 64)-NH 2 In accordance with one embodiment, each of the amino acid residues contained in the peptides is a D-amino acid residue or glycine. Although the scope of this particular embodiment is not to be limited to any theoretical reasoning, it is believed that the above-mentioned peptides, when consisting entirely of D-amino ' acid or glycine residues, may have increased resistance to proteolytic enzymes while retaining their biological activity. Such peptides thus may be administered orally. Thus in accordance with a preferred embodiment, all of the amino acid residues are either D-amino acid or glycine residues or L-ammo acid or glycine residues. An amphiphilic peptide is a peptide which includes both hydrophobic and hydrophilic peptide regions. In general, the peptides hereinabove described, and/or analogues or derivatives thereof are generally water soluble to a concentration of at least 20 mg/ml at neutral pH in water. In addition, such peptides are non-nemolytic; i.e., they will not rupture blood cells at effective concentrations. In addition, the structure of such peptide provides for flexibility of the peptide molecule. When the peptide is placed in water, it does not assume an amphiphilic structure. When the peptide encounters an oily surface or membrane, the peptide chain folds upon itself into a rod-like structure. The peptides and/or analogues or derivatives thereof may be administered to a host; for example a human or non-human animal, in an amount effective to inhibit growth of a target cell, virus, or virally-infected cell. Thus, for example, the peptides and/or analogues or derivatives thereof may be used as antimicrobial agents, anti-viral agents, antibiotics, anti-tumor agents, antiparasitic agents, antifungal agents, spermicides, as well as exhibiting other bioactive functions. The term "antimicrobial" as used herein means that the peptides of the present invention inhibit, prevent, or destroy the growth or proliferation of microbes such as bacteria, fungi, or the like. The term "antibiotic" as used herein means that the peptides employed in the present invention produce effects adverse to the normal biological functions of the non-host cell, tissue or organism, including death or destruction and prevention of the growth or proliferation of the non-host cell, tissue, or organism, when contacted with the peptides. The term "spermicidal" as used herein means that the peptides employed in the present invention, inhibit, prevent, or destroy the motility of sperm. The term "antiviral" as used herein means that the peptides employed in the present invention inhibit, prevent, or destroy the growth or proliferation of viruses, or of virally-infected cells. The term anti-tumor as used herein means that the peptide inhibits the growth of or destroys tumors. The term "antifungal" as used herein means that the peptides of the present invention may be used to inhibit the growth of or destroy fungi. The term "antiparasitic" as used herein means that the peptides of the present invention may be used to inhibit the growth of or destroy parasites. The peptides may be administered in vivo or in vitro. The peptides also may be administered directly to a target cell, virus, or virally-i fected cell, or the peptides may be administered systemically. The peptides of the present invention have a broad range of potent antibiotic activity against a plurality of microorganisms including Gram-positive and Gram-negative bacteria, fungi, protozoa, and the like, as well as parasites. The peptides of the present invention allow a method for treating or controlling microbial infection caused by organisms which are sensitive to the peptides. Such treatment may comprise administering to a host organism or tissue susceptible to or affiliated with a microbial infection an antimicrobial amount of at least one of the peptides. Because of the antibiotic, antimicrobial, and antiviral properties of the peptides, they may also be used as preservatives or sterilants of materials susceptible to micro b ial or viral contamination. The peptide and/or derivatives or analogues thereof may be administered in combination with a non-toxic pharmaceutical carrier or vehicle such as a filler, non-toxic buffer, or physiological saline solution. Such pharmaceutical compositions may be used topically or systemically and may be in any suitable form such as a liquid, solid, semi-solid, injectable solution, tablet, ointment, lotion, paste, capsule, or the like. The peptide compositions may also be used in combination with adjuvants, protease inhibitors, or compatible drugs where such a combination is seen to be desirable or advantageous in controlling infection caused by harmful microorganisms including protozoa, viruses, and the like, as well as by parasites. The peptide(s) of the present invention may be administered to a host; in particular an animal, in an effective antibiotic and/or anti-tumor and/or anti-viral and/or anti-microbial and/or anti-parasitic and/or an a tispermicidal amount. Depending on the use, a composition in accordance with the invention will contain an effective anti-microbial amount and/or an effective antispermicidal amount and/or an effective anti-viral amount and/or an effective anti-tumor amount and/or an effective antibiotic amount and/or anti-parasitic amount of one or more of the hereinabove described peptides which have such activity. The peptide of the present invention may also be employed in promoting or stimulating healing of a wound in a host. The term "wound healing" as used herein includes various aspects of the would healing process. These aspects include, but are not limited to, increased contraction of the wound, increased deposition of connective tissue, as evidenced by, for example, increased deposition of collagen in the wound, and increased tensile strength of the wound, i.e., the peptides increase wound breaking strength. The peptides of the present invention may also be employed so as t o reverse the inhibition of wound healing caused by steroids such as cortisone or by conditions which compromise or depress t h e immune system. The peptides of the present invention may be used in the treatment of external burns and to treat and/or prevent skin an d burn infections. In particular, the peptides may be used to treat skin and burn infections caused by organisms such as, b u t not limited to, P. aeruqinosa and S. aureus. The peptides are also useful in the prevention or treatment of eye infections. Such infections may be caused by bacteria such as, but not limited to, P. aeruqinosa, S. aureus, and N. gonorrhoeae, by fungi such as but not limited to C. albicans and A. fumiqatus, by parasites such as but not limited to A. castellani, or by viruses. The peptides may also be effective in killing cysts, spores, or trophozoites of infection - causing organisms. Such organisms include, but are not limited to Acanthamoeba which forms trophozoites or cysts, C. albicans, which forms spores, and A. fumiqatus, which forms spores as well. The peptides may also be administered to plants in an effective antimicrobial or antiviral or antiparasitic amount to prevent or treat microbial or viral or parasitic contamination thereof. In general, the peptide is employed to provide peptide dosages of from 0.1 mg. to 500 mg. per kilogram of host weight, when administered systemically. When administered topically, the peptide is used in a concentration of from .05% to 10%. The peptides may be produced by known techniques and obtained in substantially pure form. For example, the peptides may be synthesized on an automatic peptide synthesizer. Journal of the American Chemical Society, Vol. 85, pgs. 2149-54 (1963). It is also possible to produce such peptides by genetic engineering techniques. In accordance with another embodiment, the peptides of the present invention may be employed in combination with a toxic ion for the purposes hereinabove described. , A toxic ion is one which when introduced into a target cell , virus, or virally-infected call, inhibits and/or prevents and/or destroys the growth of the target cell, virus, or virally-infected cell. Such a toxic ion is one which in the absence of an ion channel forming peptide is unable to cross a natural or synthetic lipid membrane; in particular a cell membrane, in sufficient amounts to affect a cell adversely. The peptide and toxic ion may be administered as a single composition or in separate compositions, and the single or separate compositions may include additional materials, actives and/or inactives, in addition to the peptide and toxic ion. As representative examples of toxic ions which may be employed, there may be mentioned fluoride, peroxide, bicarbonate, and silver ions. The peptide and the toxic ion, whet z>he-_.r administered or prepared in a single composition or in separate compositions, are employed in amounts effective to inhibit and/or prevent and/or destroy the growth of the target cell, virus, or virally-infected cell. In effect, the ion potentiates the action of the peptide, i.e., the amount of toxic ion is effective to reduce the minimum effective concentration of the peptide for inhibiting growth of a target cell, virus, or virally-infected cell. The toxic ion, when used topically, is generally employed in a concentration of from 0.05% to 2.0%. When used systemically, the ion is generally employed in an amount of from 1 to 10 mg. per kg. of host weight. Peptide dosages may be within the ranges hereinabove described. It is also to be understood that the peptide and toxic ion may be delivered or administered in different forms; for example, the toxic ion may be administered orally, while the peptide may be administered by IV or IP. As representative examples of administering the peptide and toxic ion for topical or local administration, the peptide coul d be administered in an amount of up to about 1% weight to wei g ht and the toxic ion delivered in an amount of about 50mM (about 0.1%). Alternatively, the toxic ion, in the form of a salt such as sodium fluoride, could be administered orally in conjunction with systemic administration of the peptide. For example, the peptide may be administered IV or IP to achieve a serum dose of 100 micrograms per milliliter (10 milligrams per kilogram) in conjunction with an oral dose of toxic ion, in particular, sodium fluoride, of 10 meq per kilogram. In accordance with another embodiment, the peptides of the present invention may be administered to a host in combination with an antibiotic selected from the class consisting of bacitracins, gramacidin, polymyxin, vancomycin, teichoplanin, aminoglycosides, hydrophobic antibiotics, penicillins, monobactams, or derivatives or analogues thereof. The bacitracins, gramacidin, polymyxin, vancomycin, teichoplanin, and derivatives and analogues thereof, are a group of polypeptide antibiotics. A preferred bacitracin is bacitracin A. Aminoglycosidβ antibiotics include tobramycin, kanamycin, amikacin, the gentamicins (e.g., gentamicin C- L , gentamicin C 2 , gentamicin C X.C ), nβtilmicin, kanamycin, and derivatives and analogues thereof. The preferred aminoglycosides are tobramycin and the gentamicins. The aminoglycosides, and the bacitracins hereinabove described, tend to be hydrophilic and water-soluble. Penicillins which may be employed include, but are not limited to benzyl penicillin, ampicillin, methicillin (dimethoxyphenyl penicillin), ticaricillin, penicillin V (phenoxy ethyl penicillin), oxacillin, cloxacillin, dicloxacillin, .flucloxacillin, amoxicillin, and amidinocillin. Preferred penicillins which may be employed are benzyl penicillin and ampicillin. A preferred onobactam which may be employe d is aztreonam. As representative examples of hydrophobic antibiotics which may be used in the present invention, there may be mentioned macrolides such as erythromycin, roxythromycin, clarithromycm, etc.; 9-N-alkyl derivatives of erythromycin; midecamycin acetate ; azithromycin; flurithromycin; rifabutin; rokitamycin,- a 6-0-methyl erythromycin A known as TE-031 (Taisho); rifapentine . benzypiperazinyl rifamycins such as CGP-7040, CGP-5909, CGP-279353 (Ciba-Geigy); an erythromycin A derivative with a cyclic carbamate fused to the C **n/C 12 position of a macrolide ring known as A-62514 (Abbott); AC-7230 (Toyo Jozo); benzoxazinorifamycin; difficidin; dirithromycin; a 3-N-piperdinomethylzaino methyl rifamycin SV known as FCE-22250 (Farmitalia); M-119-a (Kirin Brewery); a 6-0-methyl-l-4"-0-carbamoyl erythromycin known as A-63075 (Abbott); 3-formylrifamycin SV-hydrazones with diazabicycloalkyi side chains such as CGP-27557 and CGP-2986 (Ciba-Geigy); and 16-membered macrolides having a 3-0-alpha-L-cladinosyl moiety, such as 3-0-alpha-L-cladinosyldeepoxy rosaramicin; tylosins and acyl demycinosyl tylosins. In addition to the macrolides hereinabove described, rifamycin, carbenicillin, and nafcillin may be employed as well. Other antibiotics which may be used (whether or not hydrophobic) are antibiotics which are 50-S ribosome inhibitors such as lincomycin; clindamycin; and chloramphenicol; etc.; antibiotics which have a large lipid like lactone ring, such as mystatin; pimaricin, etc. The peptide and antibiotic may be adminstered by direct administration to a target ceil or by systemic or topical administration to a host which includes the target cell, in order to prevent, destroy or inhibit the growth of a target cell. Target cells whose growth may be prevented, inhibited, or destroyed by the administration of the peptides and anti b iotic include Gram-positive and Gram-negative bacteria as well as fungal cells. The antibiotic, such as those hereinabove described, or derivatives or analogues thereof, when used topically, is generally employed in a concetration of about 0.1% to about 10%. When used systemically, the antibiotic or derivative or analogue thereof is generally employed in an amount of from 1.25 mg. to about 45 mg. per kg. of host weight per day. Peptide dosages may be those as hereinabove described. As representative exmples of administering the peptide and antibiotic for topical or local administration, the peptide could be admnistered in an amount of from about 0.1% to about 10% weight to weight, and the antibiotic is delivered in an amount of from about 0.1% to about 10% weight to weight. In accordance with another embodiment, the peptides of the present invention may be administered in combination with an antiparasitic agent or an antifungal agent. Antiparasitic agents which may be employed include, but are not limited to, anti-protozoan agents. Examples of specific anti-parasitic agents which may be employed include, but are not limited to, pentamidine isethionate, and propamidine isethionate (Brolene) . Anti-fungal agents which may be employed include, but are not limited to, ketoconazole. It is also to be understood that certain anti-parasitic agents may also have anti-fungal activity, and that certain anti-fungal agents may have anti-parasitic activity. In accordance with another embodiment, the peptides of the present invention may be administered in combination with an antibiotic which inhibits DNA gyrase, which is an enzyme involved in the formation of bonds between individual coiling strands of replicating bacterial DNA. Thus, DNA gyrase is necessary for the normal replication- of bacterial DNA, and, therefore, antibiotics which inhibit DNA gyrase inhibit the normal replication of bacterial DNA. Examples of antibiotics which inhibit DNA gyrase include nalidixic acid, oxolinic acid, cinoxacin, and quinolone antibiotics which include ciprofloxacin, norfloxacin, ofloxacm, enoxacin, pefloxacin, lomefloxacin, fleroxacin, tosulfloxacm, temafloxacin, and rufloxacin. In accordance with another embodiment, the peptides of the present invention may be administered for the purpose hereinabove described in combination with other biologically active amphiphilic peptides, or in combination with ion channel-forming proteins. Examples of biologically active amphiphilic peptides which may be employed in combination with the peptides of the present invention include magainin peptides, PGLa peptides, XPF peptides, CPF peptides, cecropins and sarcotoxins. A magainin peptide is either a magainin such as magainin I, II, or III or an analogue or derivative thereof. The magainin peptides generally include at least fourteen amino acids. A magainin peptide preferably has 22 or 23 amino acids. As representative examples of such magainin peptides, there may be mentioned peptides having the following peptide sequences as listed in the accompanying sequence listing: (a) (NH 2 ) (SEQ ID. NO: 65)(OH) or (NH 2 ) (Magainin I) (b) (NH 2 ) (SEQ ID. NO: 66)(OH) or (NH 2 ) (Magainin II) (c) (NH 2 ) (SEQ ID. NO. 67)(OH) or (NH 2 ) (Magainin III) The following are examples of peptide derivatives or analogues : (d) (NH 2 ) ( SEQ ID. NO : 68 ) (OH) or (NH 2 ) ( e ) (NH 2 ) ( SEQ ID. NO: 69 ) (OH) or (NH 2 ) ( f ) (NH 2 ) ( SEQ ID . NO : 70 ) ( OH) or (NH 2 ) Magainin peptides are described in Proc. Natl. Acad. Sci.. Vol. 84, pgs. 5449-53 (Aug. 87). The term "magainin peptides" as used herein refers to the magainin peptides as well as derivatives and analogues thereof including but not limited to the representative derivatives and analogues. A PGLa peptide is either PGLa or an analogue or derivative thereof. The PGLa peptides generally include at least seventeen amino acids and may include as many as forty amino acids. An XPF peptide is either XPF or an analogue or derivative thereof. The XPF peptides generally include at least nineteen amino acids and may include up to forty amino acids. As representative examples of PGLa and XPF peptides, there may be mentioned the following peptide sequences as well as appropriate analogues and derivatives thereof: PGLa: (SEQ ID NO: 71) ( H 2 ) XPF: (SEQ ID NO: 72) A review of XPF and PGLa can be found in Hoffman, et al., EMBO J., 2:711-714 (1983); Andreu, et al., J. Biochem, 149:531-535 (1985); Gibson, et al., J. Biol. Chem. , 261: 5341-5349 (1986); and Giovannini, et al., Biochem J. , 243:113-120 (1987). A CPF peptide is either a CPF peptide or an analogue or derivative thereof. In general, a CPF peptide does not include more than 40 amino acids. Representative examples of CPF peptides which may be employed in combination with the peptides of the present invention, some of which have been described in the literature, include the following sequences: (I) (SEQ ID NO: 73) (II) (SEQ ID NO: 74) (III) (SEQ ID NO: 75) (IV) (SEQ ID NO: 76) (V) (SEQ ID NO 77) (VI) (SEQ ID NO 78) (VII) (SEQ ID NO 79) (VIII) (SEQ ID NO 80) (IX) (SEQ ID NO 81) (X) (SEQ ID NO 82) (XI) (SEQ ID NO 83) (XII) (SEQ ID NO 84) (XIII) (SEQ ID NO 85) The above is expressed as single letter code for amino acids. A review of the CPF peptides can be found in Richter, K. , Egger, R. , and Kreil (1986) J. Biol. Chem. 261, 3676-3680; Wakabayashi, T. Kato, H. , and Tachibaba, S. (1985) Nucleic Acid's • Research 13, 1817-1828; Gibson, B.W., Poulter, L., Williams, D.H., and Maggio, J.E. (1986) J. Biol. Chem. 261, 5341-5349. The term cecropins includes the basic structure as well as analogues and derivatives thereof. The cecropins and analogues and derivatives thereof are described in Ann. Rev. Microbiol. 1987, Vol. 41, pages 103-26, in particular page 108, and in Christensen, et al., PNAS Vol. 85, pgs. 5072-76, which are hereby incorporated by reference. The term sarcotoxins includes the basic materials as well as analogues and derivatives thereof. The sarcotoxins and analogues and derivatives thereof are described in Molecular Entomology, pages 369-78, in particular page 375, Alan R. liss, Inc. (1987), which is hereby incorporated by reference. Ion channel-forming proteins or peptides which may be employed in combination with the peptides of the present invention include defensins, also known as human neutrophil antimicrobial peptides (HNP), major basic protein (MBP) of eosinophils, bactericidal permeability-increasing protein (BPI), and a pore-forming cytotoxin called variously perforin, cytolysin, or pore-forming protein. Deferisins are described in Selsted, et al., J. Clin. Invest. , Vol. 76, pgs. 1436-1439 (1985). MBP proteins are described in Wasmoen, et al., J. Biol. Chem. , Vol. 263, pgs 12559-12563. (1988). BPI proteins are described in Ooi, et al, J. Biol. Chem. , Vol. 262, pgs. 14891-14894 (1987). Perforin is described in Henkart, et al. , J. Exp. Med. , 160: 75 (1984), and in Podack, et al., J. E XP . Me d 160:695 (1984). The above articles are hereby incoroporated b y reference. The term ion channel-forming proteins includes the basic structures of the ion-forming proteins as well as analogues and derivatives. The invention will now be further described with respect to the following examples; however, the scope of the present invention is not to be limited thereby. ■Example 1 - Antibacterial Assay The procedure for the following antibacterial assay is based upon the guidelines of the National Committee for Clinical Laboratory Standards, Document M7-T2, Volume 8, No. 8, 1988. Stock solutions of the following Peptides (SEQ ID NO: 1) through (SEQ ID NO:- 64) in accordance with the present invention are prepared at a concentration of 512 μg/ml in sterile deionized distilled water and stored at -70 β C. Peptide (1A) is of the same structural formula as Peptide (SEQ ID NO: 1), except that each amino acid residue is a D-amino acid residue. The stock peptide solution is diluted in serial dilutions (1:2) down the wells of a microtiter plate so that the final concentrations of peptides in the wells are 0.25, 0.50, 1, 2, 4, 8, 16, 32, 64, 128, and 256 μg/ml. 1-5 X 10 5 CFUs/ml of either S. aureus ATCC 25923, E. coli ATCC 25922, or P. aeruqinosa ATCC 27853 were added to the wells in full strength Mueller Hinton broth (BBL 11443) from a mid-log culture. The inoculum is standarized spectrophotometrically at 600nm and is verified by colony counts. The plates are incubated for 16-20 hours at 37°C, and the minimal inhibitory concentration (MIC) for each peptide is determined. Minimal inhibitory concentration is defined as the lowest concentration of peptide which produces a clear well in the microtiter plate. The results are given in Table I below. For purposes of explanation of Table I below, S is the MIC of the peptide against S.aureus, P is the MIC of the peptide against P.aeruqinosa, and E is the MIC of the peptide against E.coli. TABLE I Peptide (SEQ ID NO:l) (1A) (SEQ ID NO:2) (SEQ ID NO:3) (SEQ ID NO:4) (SEQ ID NO:5) (SEQ ID NO:6) (SEQ ID NO:7) (SEQ ID NO:8) (SEQ ID NO:9) (SEQ ID NO:10) (SEQ ID NO:11) (SEQ ID NO:12) (SEQ ID NO:13) (SEQ ID NO:14) (SEQ ID NO:15) (SEQ ID NO:16) (SEQ ID NO:17) (SEQ ID NO:18) (SEQ ID NO:19) (SEQ ID NO:20) (SEQ ID NO:21) (SEQ ID NO:22) 128 4,8 128 8 32 2 16 4 128,256 8,16 128 8 128 4,8 32,64 8,16 Example 2 - Antiparasitic Assay Logarithmic phase axenic cultures of Acanthamoeba polyphaσa trophozoites were grown at 30 β C in fluid ppyg medium (2% proteose-peptone; 0.5% yeast extract; 0.5% glucose; pH 7.2). Cells were counted using a Coulter counter, and added to fresh ppyg medium to give a cell concentration of approximately 10,000 amoebas/ml. Cell suspensions were then transferred to Corning tissue culture flasks (25 cm 3) to which either Peptide (SEQ ID NO:l) or Peptide (SEQ ID NO:43) had been added to appropriate concentrations, with each flask containing 10ml of medium. The flasks were incubated at 30°C. 0.5ml samples were removed from the flasks, generally over a 5-day period, for counting in a Coulter Counter. For determination of Minimum Inhibitory Concentration (MIC) and Minimum Amoebicidal Concentration (MAC) of the trophozoites, the contents of appropriate flasks were centrifuged, washed free of "old" medium and peptide with dilute saline, resuspended in fresh ppyg medium, and transferred to Corning tissue culture tubes (16 X 125mm). The tubes were incubated at 30°C and examined at daily intervals for growth of amoebas. Minimum Amoebicidal Concentration is defined is the minimum concentration of peptide necessary to kill the trophozoites. The results are given in Table II below. TABLE II Anti p arasitic Activity Against Acanthamoeba polyphaqa Trophozoites Peptide MIC MAC (SEQ ID NO:l) 20 25 (SEQ ID NO:43) 25 40 The peptides of the present invention, whether administered alone or in combination with agents such as toxic ions, antibotics, or other biologically active peptides or proteins as hereinabove described, may be employed in a wide variety of pharmaceutical compositions in combination with a non-toxic pharmaceutical carrier or vehicle such as a filler, non-toxic buffer, or physiological saline solution. Such pharmaceutical compositions may be used topically or systemically and may be in any suitable form such as a liquid, solid, semi-solid, injectable solution, tablet, ointment, lotion, paste, capsule or the like. The peptide and/or agent as hereinabove described may also be used in combination with adjuvants, protease inhibitors, or compatible drugs where such a combination is seen to be desirable or advantageous in controlling infection caused by harmful microorganisms including protozoa, viruses, parasites, fungi, and the like. The peptide may be administerd to a host in particular an animal, in an effective antibiotic and/or anti-tumor and/or antiviral and/or antimicrobial and/or antispermicidal and/or antifungal and/or antiparasitic amount, or in an amount effective to stimulate wound healing in a host. The peptides may be administerd either alone or in combination with a toxic ion, antibiotic, or ion channel forming peptide or protein as hereinabove described. When the peptide is administered in combination with a toxic ion, the activity of the peptide is potentiated. When the peptide is administered in combination with an agent as hereinabove described, it is possible to administer the peptide and agent in separate forms. For example, the agent may be administered systemically and the peptide may be administere d topically. When the peptide is ad initered topically, it may be administered in combination with a water-soluble vehicle, said water-soluble vehicle being in the form of an ointment, cream, lotion, paste or the like. Examples of water-soluble vehicles which may be employed include, but are not limited to, glycols, such as polyethylene glycol, hydroxycellulose, and KY Jelly. The water-soluble vehicle is preferably free of an oily substance. The peptide may also be employed in combination with a toxic ion as hereinabove described in the form of an oral composition for oral hygiene. Such a composition may be incorporated into a wide variety of compositions and materials used for oral hygiene purposes, which include, but are not limited to, toothpastes, mouthwashes, tooth gels, and tooth powders. " Such composition may thus be used to treat or prevent periodontal disease, to prevent or reduce plaque, and/or to prevent or treat or reduce dental caries. The peptide and toxic ion may be used to inhibit, prevent, or destroy the growth of Streptococcus mutans, which is associated with dental caries and periodontal disease. Numerous modifications and variations of the present invention are possible in light of the above teachings and, therefore, within the scope of the accompanying claims, the invention may be practiced other than as particularly described. SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: Berkowitz, Barry A. Kari, U. Prasad Maloy, W. Lee (ii) TITLE OF INVENTION: Novel Peptide Compositions and Uses Therefore (iii) NUMBER OF SEQUENCES: 85 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: Carella, Byrne, Bain, Gilfillan, Cecchi & Stewart (B) STREET: 6 Becker Farm Road (C) CITY: Roseland (D) STATE: New Jersey (E) COUNTRY: USA (F) ZIP: 07068 (V) COMPUTER READABLE FORM: (A) MEDIUM TYPE: 3.5 inch diskette (B) COMPUTER: IBM PS/2 (C) OPERATING SYSTEM: PC-DOS (D) SOFTWARE: DW4.V2 (vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: US 07476629 (B) FILING DATE: 08-FEB-1990 (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: lstein, Elliot M. (B) REGISTRATION NUMBER: 24,025 (C) REFERENCE/DOCKET NUMBER: 421250-122 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: 201-994-1700 (B) TELEFAX: 201-994-1744 (2) INFORMATION FOR SEQ ID N0:1 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Lys He Ala Lys He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:2 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( ix ) FEATURE : (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: Lys He Ala Lys He Ala Gly Lys He Ala 5 10 Lys He Ala Gly Lys He Ala Lys He Ala 15 20 Gly (2) INFORMATION FOR SEQ ID NO:3 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: Lys He Ala Gly Lys He Gly Lys He Ala 5 10 Gly Lys He Gly Lys He Ala Gly Lys He 15 20 Gly (2) INFORMATION FOR SEQ ID NO:4 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( ix ) FEATURE : (D) OTHER INFORMATION: amide-terminated ( i) SEQUENCE DESCRIPTION: SEQ ID NO: : Lys Leu Ala Gly Lys Leu Ala Lys Leu Ala 5 10 Gly Lys Leu Ala Lys Leu Ala Gly Lys Leu 15 20 Ala (2) INFORMATION FOR SEQ ID NO:5 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: Lys Phe Ala Gly Lys Phe Ala Lys Phe Ala 5 10 Gly Lys Phe Ala Lys Phe Ala Gly Lys Phe 15 20 Ala (2) INFORMATION FOR SEQ ID NO:6 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: Lys Ala Leu Ser Lys Ala Leu Lys Ala Leu 5 10 Ser Lys Ala Leu Lys Ala Leu Ser Lys Ala 15 20 Leu (2) INFORMATION FOR SEQ ID NO:7 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: Lys Leu Leu Lys Ala Leu Gly Lys Leu Leu 5 10 Lys Ala Leu Gly Lys Leu Leu Lys Ala Leu 15 20 Gly (2) INFORMATION FOR SEQ ID NO:8 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino.acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: Lys Ala He Gly Lys Ala He Lys Ala He 5 10 Gly Lys Ala He Lys Ala He Gly Lys Ala 15 20 He (2) INFORMATION FOR SEQ ID NO:9 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: Gly He Ala Lys He Ala Lys Gly He Ala 5 10 Lys He Ala Lys Gly He Ala Lys He Ala 15 20 Lys (2) INFORMATION FOR SEQ ID NO:10 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: Lys He Ala Lys He Phe Gly Lys He Ala 5 10 Lys He Phe Gly Lys He Ala Lys He Phe 15 20 Gly (2) INFORMATION FOR SEQ ID NO:11 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: Gly He Ala Arg He Ala Lys Gly He Ala 5 10 Arg He Ala Lys Gly He Ala Arg He Ala 15 20 Lys (2) INFORMATION FOR SEQ ID NO:12 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: Lys Phe Ala Arg He Ala Gly Lys Phe Ala 5 10 Arg He Ala Gly Lys Phe Ala Arg He Ala 15 20 Gly (2) INFORMATION FOR SEQ ID NO:13 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: Gly Phe Ala Lys He Ala Lys Gly Phe Ala 5 10 Lys He Ala Lys Gly Phe Ala Lys He Ala 15 20 Lys (2) INFORMATION FOR SEQ ID NO:14 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: Lys He Ala Gly Orn He Ala Lys lie Ala 5 10 Gly Orn He Ala Lys He Ala Gly Orn He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:15 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: Lys He Ala Arg He Ala Gly Lys He Ala 5 10 Arg He Ala Gly Lys He Ala Arg He Ala 5 20 Gly (2) INFORMATION FOR SEQ ID NO: 16 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: Orn He Ala Gly Lys He Ala Orn He Ala 5 10 Gly Lys He Ala Orn He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:17 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: Gly He Ala Arg He Phe Lys Gly He Ala 5 10 Arg He Phe Lys Gly He Ala Arg He Phe 15 20 Lys (2) INFORMATION FOR SEQ ID NO:18 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: Lys Nle Ala Gly Lys Nle Ala Lys Nle Ala 5 10 Gly Lys Nle Ala Lys Nle Ala Gly Lys Nle 15 20 Ala (2) INFORMATION FOR SEQ ID NO:19 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: Lys Nle Ala Gly Lys He Ala Lys Nle Ala 5 10 Gly Lys He Ala Lys Nle Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:20 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: Lys He Ala Gly Lys Nle Ala Lys He Ala 5 10 Gly Lys Nle Ala Lys He Ala Gly Lys Nle 15 20 Ala (2) INFORMATION FOR SEQ ID NO:21 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: Lys Nva Ala Gly Lys Nva Ala Lys Nva Ala 5 10 Gly Lys Nva Ala Lys Nva Ala Gly Lys Nva 15 20 Ala (2) INFORMATION FOR SEQ ID NO:22 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: Lys Nva Ala Gly Lys He Ala Lys Nva Ala 5 10 Gly Lys He Ala Lys Nva Ala Gly Lys Nva 15 20 Ala (2) INFORMATION FOR SEQ ID NO:23 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: Lys Leu Leu Ser Lys Leu Gly tys Leu Leu 5 10 Ser Lys Leu Gly Lys Leu Leu Ser Lys Leu 15 20 Gly (2) INFORMATION FOR SEQ ID NO:24 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: Lys Leu Leu Ser Lys Phe Gly Lys Leu Leu 5 10 Ser Lys Phe Gly Lys Leu Leu Ser Lys Phe 15 20 Gly (2) INFORMATION FOR SEQ ID NO:25 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: Lys He Ala Gly Lys Nva Ala Lys He Ala 5 10 Gly Lys N\ * Ala Lys He Ala Gly Lys Nva 15 20 Ala (2) INFORMATION FOR SEQ ID NO:26 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: His He Ala Gly His He Ala His He Ala 5 10 Gly His He Ala His He Ala Gly His He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:27 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: Ala Gly Lys He Ala Lys He Ala Gly Lys 5 10 He Ala Lys He Ala Giy Lys He Ala Lys 15 20 He (2) INFORMATION FOR SEQ ID NO:28 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear. (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: He Ala Lys He Ala Gly Lys He Ala Lys 5 10 He Ala Gly Lys He Ala Lys He Ala Gly 15 20 Lys (2) INFORMATION FOR SEQ ID NO:29 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: Lys He Ala Gly Arg He Ala Lys He Ala 5 10 Gly Arg He Ala Lys He Ala Gly Arg He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:30 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear. (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: Arg He Ala Gly Arg He Ala Arg He Ala 5 10 Gly Arg He Ala Arg He Ala Gly Arg He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:31 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: Lys Val Ala Gly Lys He Ala Lys Val Ala 5 10 Gly Lys He Ala Lys Val Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:32 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE; amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: Lys He Ala Gly Lys Val Ala Lys He Ala 5 10 Gly Lys Val Ala Lys He Ala Gly Lys Val 15 20 Ala (2) INFORMATION FOR SEQ ID NO:33 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: Ala Lys He Ala Gly Lys He Ala Lys He 5 10 Ala Gly Lys He Ala Lys He Ala Gly Lys 15 20 He (2) INFORMATION FOR SEQ ID NO:34 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: Orn He Ala Gly Orn He Ala Orn He Ala 5 10 Gly Orn He Ala Orn He Ala Gly Orn He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:35 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: Lys Phe Ala Gly Lys He Ala Lys Phe Ala 5 10 Gly Lys He Ala Lys Phe Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:36 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: Lys He Ala Gly Lys Phe Ala Lys He Ala 5 10 Gly Lys Phe Ala Lys He Ala Gly Lys Phe 15 20 Ala (2) INFORMATION FOR SEQ ID NO:37 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( ix ) FEATURE : (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: Lys Cha Ala Gly Lys He Ala Lys Cha Ala 5 10 Gly Lys He Ala Lys Cha Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:38 (i) SEQUENCE CHARACTERISTICS ( A) LENGTH: 21 aπiino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: Lys Nle Ala Lys He Ala Gly Lys Nle Ala 5 10 Lys He Ala Gly Lys Nle Ala Lys He Ala 15 20 Gly (2) INFORMATION FOR SEQ ID NO:39 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 -amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: Arg He Ala Gly Lys He Ala Arg He Ala 5 10 Gly Lys He Ala Arg He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:40 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:40: Har He Ala Gly Har He Ala Har He Ala 5 10 Gly Har He Ala Har He Ala Gly Har He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:41 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: amide-terminated, Xaa is p-aminophenylalanine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: Xaa He Ala Gly Lys He Ala Xaa He Ala 5 10 Gly Lys He Ala .Xaa He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:42 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: amide-terminated, Xaa is p-aminophenylalanine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: Lys He Ala Gly Xaa He Ala Lys He Ala 5 10 Gly Xaa He Ala Lys He Ala Gly Xaa He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:43 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: Lys Leu Ala Ser Lys Ala Gly Lys He Ala Gly 5 10 Lys He Ala Lys Val Ala Leu Lys Ala Leu 15 20 (2) INFORMATION FOR SEQ ID NO:44 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: Lys He Ala Gly Lys He Ala Lys He Ala Gly 5 10 Orn He Ala Lys He Ala Gly Lys He Ala 15 20 (2) INFORMATION FOR SEQ ID NO:45 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Arg He Ala Lys He Ala Gly Lys He 15 ' 20 Ala (2) INFORMATION FOR SEQ ID NO:46 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Nle He Ala Lys He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:47 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: .21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Nva He Ala Lys He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:48 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: Lys Phe Ala Gly Lys Phe Ala Lys Phe Ala Gly 5 10 Orn Phe Ala Lys Phe Ala Gly Lys Phe Ala 15 20 (2) INFORMATION FOR SEQ ID NO:49 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: Lys, He Ala Gly Lys Phe Ala Lys He Ala 5 10 Gly Orn Phe Ala Lys He Ala Gly Lys Phe 15 20 Ala (2) INFORMATION FOR SEQ ID NO:50 (i) SEQUENCE CHARACTERISTICS ■ (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated ( i) SEQUENCE DESCRIPTION: SEQ ID NO:50: Lys He Ala Gly Lys Nle Ala Lys He Ala 5 10 Gly Orn Nle Ala Lys He Ala Gly Lys Nle 15 20 Ala (2) INFORMATION FOR SEQ ID NO:51: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-termianted (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51: Lys Met Ala Ser Lys Ala Gly Lys He Ala 5 10 Gly Lys He Ala Lys Val Ala Leu Lys Ala 15 20 Leu (2) INFORMATION FOR SEQ ID NO:52: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52 Lys He Ala Ser Lys Ala Gly Lys He Ala 5 10 Gly Lys He Ala Lys Val Ala Leu Lys Ala Leu 15 20 (2) INFORMATION FOR SEQ ID NO:53: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:53: Lys He Ala Ser Lys Ala Gly Lys Nle Ala 5 10 Gly Lys He Ala Lys Val Ala Leu Lys Ala 15 20 Leu (2) INFORMATION FOR SEQ ID NO:54: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: Lys Leu Ala Ser Lys Ala Gly Lys Nle Ala 5 10 Gly Lys He Ala Lys Val Ala Leu Lys Ala 15 • 20 Leu (2) INFORMATION FOR SEQ ID NO:55: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:55: Lys Nle Ala Ser Lys Ala Gly Lys Nle Ala 5 10 Gly Lys He Ala Lys Val Ala Leu Lys Ala Leu 15 20 (2) INFORMATION FOR SEQ ID NO:56 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated, Xaa is p-aminophenylalanine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:56: Lys He Ala Gly Lys He Ala Lys He Ala 5 " 10 Gly Xaa He Ala Lys He Ala Gly Lys He 15 Ala (2) INFORMATION FOR SEQ ID NO:57 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:57: Lys He Ala Gly Ala He Ala Lys He Ala 5 10 Gly Lys He Ala Lys He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:58 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:58: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Ala He Ala Lys He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:59 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:59: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Lys He Ala Lys He Ala Gly Ala He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:60 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 -amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:60: Lys He Ala Lys Lys He Ala Lys He Ala 5 10 Lys Lys He Ala Lys He Ala Lys Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:61 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:61: Ala He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Lys He Ala Lys He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:62 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:62: Lys He Ala Gly Lys He Ala Ala He Ala 5 10 Gly Lys He Ala Lys He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:63 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:63: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Lys He Ala Ala He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:64 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: amide-terminated (xi) SEQUENCE DESCRIPTION: SEQ ID NO:64: Gly Met Ala Ser Lys Ala Gly Lys He Ala 5 10 Gly Lys He Ala Lys Val Ala Leu Lys Ala 15 20 Leu (2) INFORMATION FOR SEQ ID NO:65 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 23 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: Magainin I peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proceedings of the National Academy of Sciences (D) VOLUME: 84 (F) PAGES: 5449-5453 (G) DATE: AUG - 1987 (H) DOCUMENT NUMBER: US 4810777 (I) FILING DATE: 04-MAR-1987 (J) PUBLICATION DATE: 07-MAR-1989 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:65 Gly He Gly Lys Phe Leu His Ser Ala Gly 5 10 Lys Phe Gly Lys Ala Phe Val Gly Glu lie 15 20 Met Lys Ser (2) INFORMATION FOR SEQ ID NO:66 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 23 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: Magainin II peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proceedings of the National Academy of Sciences (D) VOLUME: 84 (F) PAGES: 5449-5453 (G) DATE: AUG - 1987 (H) DOCUMENT NUMBER: US 4810777 (I) FILING DATE: 04-MAR-1987 (J) PUBLICATION DATE: 07-MAR-1989 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:66 Gly He Gly Lys Phe Leu His Ser Ala Lys 5 10 Lys Phe Gly Lys Ala Phe Val Gly Glu He 15 20 Met Asn Ser (2) INFORMATION FOR SEQ ID NO:67 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 22 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: Magainin III peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proceedinqs of the National Academy of Sciences (D) VOLUME: 84 (F) PAGES: 5449-5453 (G) DATE: AUG - 1987 (H) DOCUMENT NUMBER: US 4810777 (I) FILING DATE: 04-MAR-1987 (J) PUBLICATION DATE: 07-MAR-1989 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:67: Gly He Gly Lys Phe Leu His Ser Ala Lye 5 10 Lys Phe Gly Lys Ala Phe Val Gly Glu He 15 20 Met Asn (2) INFORMATION FOR SEQ ID NO:68 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 22 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: magainin peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proceedings of the National Academy of Sciences (D) VOLUME: 84 (F) PAGES: 5449-5453 (G) DATE: AUG - 1987 (H) DOCUMENT NUMBER: US 4810777 (I) FILING DATE: 04-MAR-1987 (J) PUBLICATION DATE: 07-MAR-1989 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:68: He Gly Lys Phe Leu His Ser Ala Lys Lys 5 10 Phe Gly Lys Ala Phe Val Gly Glu He Met 15 20 Asn Ser (2) INFORMATION FOR SEQ ID NO:69 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: magainin peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proceedings of the National Academy of Sciences (D) VOLUME: 84 . (F) PAGES: 5449-5453 (G) DATE: AUG - 1987 (H) DOCUMENT NUMBER: US 4810777 (I) FILING DATE: 04-MAR-1987 (J) PUBLICATION DATE: 07-MAR-1989 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:69: Gly Lys Phe Leu His Ser Ala Lys Lys Phe 5 10 Gly Lys Ala Phe Val Gly Glu He Met Asn 15 20 Ser (2) INFORMATION FOR SEQ ID NO:70 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 20 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: magainin peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proceedings of the National Academy of Sciences (D) VOLUME: 84 (F) PAGES: 5449-5453 (G) DATE: AUG - 1987 (H) DOCUMENT NUMBER: US 4810777 (I) FILING DATE: 04-MAR-1987 (J) PUBLICATION DATE: 07-MAR-1989 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:70: Lys Phe Leu His Ser Ala Lys Lys Phe Gly 5 10 Lys Ala Phe Val Gly Glu He Met Asn Ser 15 20 (2) INFORMATION FOR SEQ ID NO:71 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: PGLa peptide. (D) OTHER INFORMATION: amide-terminated (X) PUBLICATION INFORMATION: (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71: Gly Met Ala Ser Lys Ala Gly Ala He Ala 5 10 Gly Lys He Ala Lys Val Ala Leu Lys Ala 15 20 Leu (2) INFORMATION FOR SEQ ID NO:72 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 25 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: XPF peptide. (X) PUBLICATION INFORMATION: (A) AUTHOR: Hoffman, et al.1 (C) JOURNAL: EMBO J. (D) VOLUME: 2 (F) PAGES: 711-714 (G) DATE: 1983 (A) AUTHOR: Andreu, et al. (C) JOURNAL: Journal of Biochemistry (D) VOLUME: 149 (F) PAGES: 531-535 (G) DATE: 1985 (A) AUTHOR: Gibson, et al. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 5341-5349 (G) DATE: 1986 (A) AUTHOR: Giovannini, et al. (C) JOURNAL: Biochem J. (D) VOLUME: 243 . (F) PAGES: 113-120 (G) DATE: 1987 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:72: Gly Trp Ala Ser Lys He Gly Gin Thr Leu 5 10 Gly Lys He Ala Lys Val Gly Leu Lys Glu 15 20 Leu He Gin Pro Lys 25 (2) INFORMATION FOR SEQ ID NO:73 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Kreil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (C) JOURNAL: Nucleic Acids Research (D) VOLUME: 13 (F) PAGES: 1817-1828 (G) DATE: 1985 (A) AUTHOR: Gibson, B.W. Poulter, L. Williams, D.H. Maggio, J.E. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 5341-5349 (G) DATE : 1986 (H) DOCUMENT NUMBER: W090/04407 (I) FILING DATE: 16-OCT-1989 (J) PUBLICATION DATE: 03-MAY-1990 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:73: Gly Phe Gly Ser Phe Leu Gly Leu Ala Leu 5 10 Lys Ala Ala Leu Lys He Gly Ala Asn Ala 15 20 Leu Gly Gly Ala Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:74 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K Egger, R. Kreil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. (xi)' SEQUENCE DESCRIPTION: SEQ ID NO:74 Gly Leu Ala Ser Phe Leu Gly Lys Ala Leu 5 10 Lys Ala Gly Leu Lys He Gly Ala His Leu 15 20 Leu Gly Gly Ala Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:75 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( ix ) FEATURE : (A) NAME/KEY: CPF peptide. ( D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:75: Gly Leu Ala Ser Leu Leu Gly Lys Ala Leu 5 10 Lys Ala Gly Leu Lys He Gly Thr His Phe 15 20 Leu Gly Gly Ala Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:76 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Kreil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 (G) DATE: . 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (C) JOURNAL: Nucleic Acids Research (D) VOLUME: 13 (F) PAGES: 1817-1828 (G) DATE: 1985 (A) AUTHOR: Gibson, B.W. Poulter, L. Williams, D.H. - Maggio, J.E. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 5341-5349 (G) DATE: 1986 (H) DOCUMENT NUMBER: W090/04407 (I) FILING DATE: 16-OCT-1989 (J) PUBLICATION DATE: 03-MAY-1990 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76: Gly Leu Ala Ser Leu Leu Gly Lys Ala Leu 5 10 Lys Ala Thr Leu Lys He Gly Thr His Phe 15 20 Leu Gly Gly Ala Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:77 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Kreil (xi) SEQUENCE DESCRIPTION: SEQ ID NO:77 Gly Phe Ala Ser Phe Leu Gly Lys Ala Leu 5 10 Lys Ala Ala Leu Lys He Gly Ala Asn Met 15 20 Leu Gly Gly Thr Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:78 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER INFORMATION: amide- or carboxy- terminate d (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. (J) PUBLICATION DATE: 03-MAY-1990 ( i) SEQUENCE DESCRIPTION: SEQ ID NO:78: Gly Phe Gl ' y Ser Phe Leu Gly Lys Ala Leu 5 10 Lys Ala Ala Leu Lys He Gly Ala Asn Ala 15 20 Leu Gly Gly Ala Pro Gin Gin 25 (2) INFORMATION. FOR SEQ ID NO:79 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER- INFORMATION: amide- or carboxy- terminated (X) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Kreil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (C) JOURNAL: Nucleic Acids Research (D) .VOLUME:. 13 (F) PAGES: 1817-1828 (G) DATE: 1985 (A) AUTHOR: Gibson, B.W. Poulter, L. Williams, D.H. Maggio, J.E. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 5341-5349 (G) DATE: 1986 (H) DOCUMENT NUMBER: W090/04407 (I) FILING DATE: 16-0CT-1989 (J) PUBLICATION DATE: 03-MAY-1990 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:79: Gly Phe Gly Ser Phe Leu Gly Lys Ala Leu 5 10 Lys Ala Ala Leu Lys He Gly Ala Asn Ala 15 20 Leu Gly Gly Ser Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:80 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated -80- (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Kreil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (C) JOURNAL: Nucleic Acids Research (D) VOLUME: 13 (F) PAGES: 1817-1828 (G) DATE: 1985 (A) AUTHOR: Gibson, B.W. • » Poulter, L. Williams, D.H. Maggio, J.E. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 5341-5349 (G) DATE: 1986 (H) DOCUMENT NUMBER: W090/04407 (I) FILING DATE: 16-OCT-1989 ( J ) PUBLICATION DATE: 03-MAY-1990 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:80: Gly Phe Ala Ser Phe Leu Gly Lys Ala Leu 5 10 Lys Ala Ala Leu Lys He Gly Ala Asn Leu 15 20 Leu Gly Gly Thr Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:81 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Kreil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (C) JOURNAL: Nucleic Acids Research (D) VOLUME: 13 (F) PAGES: 1817-1828 (G) DATE: 1985 (A) AUTHOR: Gibson, B.W. Poulter, L. Williams, D.H. Maggio, J.E. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 5341-5349 (G) DATE: 1986 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:81: Gly Phe Ala Ser Phe Leu Gly Lys Ala Leu 5 10 Lys Ala Ala Leu Lys He Gly Ala Asn Ala 15 20 Leu Gly Gly Ala Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:82 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. . (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Kreil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (C) JOURNAL: Nucleic Acids Research (D) VOLUME: 13 (F). PAGES: 1817-1828 (G) DATE : 1985 (A) AUTHOR: Gibson, B.W. Poulter, L. Williams, D.H. Maggio, J.E. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 5341-5349 (G) DATE: 1986 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:82: Gly Phe Ala Ser Phe Leu Gly Lys Ala Leu 5 10 Lys Ala Ala Leu Lys He Gly Ala Asn Met 15 20 Leu Gly Gly Ala Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:83 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER INFORMATION: amide- or carboxy- terminated (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Krβil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (C) JOURNAL: Nucleic Acids Research (D) VOLUME: 13 (F) PAGES: 1817-1828 (G) DATE: 1985 (A) AUTHOfe: Gibson, B.W. Poulter, L. Williams, D.H. Maggio, J.E. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 5341-5349 (G) DATE: 1986 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:83: Gly Phe Gly Ser Phe Leu Gly Lys Ala Leu 5 10 Lys Ala Ala Leu Lys He Gly Ala Asn Ala 15 20 Leu Gly Gly Ser Leu Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:84 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 -amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER INFORMATION: amide- or carboxy- terminate (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Kreil (C) JOURNAL: J. Biol. Chem (D) VOLUME: 261 (F) PAGES: 3676,-3680 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (C) JOURNAL; Nucleic Acids Research (D) VOLUME: 13 (F) PAGES: 1817-1828 (G) DATE: 1985 (A) AUTHOR: Gibson, B.W. Poulter, L. Williams, D.H. Maggio, J.E. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 5341-5349 (G) DATE: 1986 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:84: Gly Phe Gly Ser Phe Leu Gly Lys Ala Leu 5 10 Lys Ala Gly Leu Lys He Gly Thr Asn Phe 15 20 Leu Gly Gly Ala Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:85 (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (D) OTHER INFORMATION: amide- or carboxy- terminate d (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K Egger, R. Kreil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (C) JOURNAL: Nucleic Acids Research (D) VOLUME: 13 (F) PAGES: 1817-1828 (G) DATE: 1985 (A) AUTHOR: Gibson, B.W. Poulter, L. Williams, D.H. Maggio, J.E. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES : 5341-5349 (G) DATE: 1986 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:85 Gly Leu Ala Ser Leu Leu Gly Lys Ala Leu 5 10 Lys Ala Ala Leu Lys He Gly Ala Asn Ala 15 20 Leu Gly Gly Ser Pro Gin Gin 25

Claims: WHAT IS CLAIMED IS: 1. A biologically active amphiphilic peptide, said peptide including one of the following basic structures X-, through X wherein X l is - f n' x 2 is -tR 2 -R 2 -R 3 -R 1 -R 2 -R 2 -R 1 l- n X 3 is "lR 2 "R 3 -R l "R 2 'R 2 "'R l "R 2 " n x 4 is - ( 3 - 1 - 2 -R 2 -Rι- 2 - 2 ]- n x 5 is -tR 1 -R 2 -R 2 -R 1 -R 2 -R 2 -R 3 ]- n X 6 is -{R 2 -R 2 -R 1 -R 2 -R 2 -R 3 -R 1 l- n ; and X 7 is -tR 2 -R 1 -R 2 -R 2 -R 3 -R 1 -R 2 ]- n wherein 1 is a basic hydrophilic amino acid, R 2 is a hydrophobic amino acid, R 3 is a neutral hydrophilic or hydrophobic amino acid, and n is from 2 to 5. 2. The peptide of Claim 1 wherein n is 3. 3. The peptide of Claim 2 wherein said peptide has the following structural formula: (Lys He Ala Gly Lys He Ala) 3 -NH 2 4. The. peptide of Claim 2 wherein said peptide has the following structural formula: (Lys He Ala Lys He Ala Gly) 3 -NH 2 5. A composition comprising the peptide of Claim 1, and a pharmaceutical carrier. 6. The composition of Claim 5 wherein said peptide is present in an amount effective to inhibit growth of a target cell. 7. A process for inhibiting growth of a target cell, virus, or virally-infected cell, comprising: administering a biologically active amphiphilic peptide, said peptide including one of the following basic structures X 1 through X 7 , wherein: x l is -l*! "1 ^ " ^ " ^ " *! " ^ " ^ 1" ^ X 2 is " [R 2- R 2" R 3 'R l 'R 2 'R 2 "R l ]" n ; X 3 is -[R 2 -R3- R l- R 2- R 2- R l- R 2 ] -n ; X 4 is - l R 3 .R 1 -R 2 -R 2 -R 1 -R 2 -R 2 ] - n X 5 is " ( R ^-W W ^ ^ n X 6 is - [ R 2 _R 2 -R 1 - 2 -R 2 -R 3 -R 1 ] - n and X 7 is "f R 2- R l "R 2 "R 2 "R 3~ R l "" 2'~n ; wherein R 1 is a basic hydrophilic amino acid, R is a hydrophobi amino acid, R 3 is a neutral hydrophilic, basic hydrophilic, or hydrophobic amino acid, and n is from 2 to 5. 8. The process of Claim 7 wherein n is 3. 9. The process of Claim 8 wherein said peptide has the following structural formula: (Lys He Ala Gly Lys He Ala) 3 «NH 2 . 10. The process of Claim 8 wherein said peptide has the following structural formulae (Lys He Ala Lys He Ala Gly) 3 -NH 2 . 11. The process of Claim 7 wherein said administering is t an animal host in an effective anti- umor amount. 12. The process of Claim 7 wherein said administering is t an animal host in an effective anti-viral amount. 13. The process of Claim 7 wherein said administering is t an animal host in an effective antimicrobial amount. 14. The process of Claim 7 wherein said administering is t an animal host in an effective anti-parasitic amount. 15. The process of Claim 7 wherein said administering is t an animal host in an effective antibiotic amount. 16. The process of Claim 7 wherein said administering is t an animal host in an effective anti-spermicidal amount. 17. The process of Claim 7 wherein said administering is t an animal host in an amount effective in treating healing of a wound in said animal host. 18. A biologically active amphiphilic peptide, said peptid including the following basic structure: X 14 R 1 -R 2 -R 2 -R 3 -R 4 -R 2 -R 2 -R 1 -R 2 -R 2 -R 2 -R 4 -R 2 -R 2> wherein R χ is a basic hydrophilic amino acid, R £ is a hydrophob amino acid, R 3 is a neutral hydrophilic or a hydrophobic amino acid, and R 4 is a basic hydrophilic or hydrophobic amino acid. 19. The peptide of Claim 26 wherein the peptide inclu d es the following structure: Y 14" X 14' wherein x i4 is the basic peptide structure of Cla 18, and Y- 4 is: (i) R 2 ; (ii) R 2 -R 2 ; (iii) R 4 -R 2 -R 2 ; (iv) R 3 -R 4 -R 2 -R 2 ; (V) R 2 -R 3 -R 4 -R 2 -R 2 ; (Vi) R 2 -R 2 -R 3 -R 4 -R 2 -R 2 ; or (Vii) R 1 -R 2 -R 2 -R 3 -R 4 -R 2 -R 2 . 20. The peptide of Claim 18 wherein the peptide includes the following structure: 14 -Z 14 , wherein X 14 is the basic peptide structure of Cla 18 and Z-. is: (i) R χ ; (ii) j - ^ (iii) R 1 -R 2 -R 2 ; (iv) R 1 -R 2 -R 2 -R 3 ; (V) R 1 -R 2 -R 2 -R 3 -R 4 ; (Vi) R 1 -R 2 -R 2 -R 3 -R 4 -R 2 ; or (vii) R 1 -R 2 -R 2 -R 3 -R 4 -R 2 -R 2 . 21. The peptide of Claim 18 wherein the peptide includes the following basic structure: (Y 14 )a-(X 14 )-(Z- 4 )b, wherein Y 14 and Z 14 are as previuosly described in Claims 19 and 20, a is 0 or 1 and b is 0 or 1. 22. The peptide of Claim 21 wherein said peptide has the following structural formula: Lys Leu Ala Ser Lys Ala Gly Lys He Ala Gly Lys 5 10 He Ala Lys Val Ala Leu Lys Ala Leu - NH 2 15 20 23. The peptide of Claim 21 wherein said peptide has the following structural formula: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Orn He Ala Lys He Ala Gly Lys He 15 20 Ala - NH- 24. A composition comprising the peptide of Claim 18 and a pharmaceutical carrier. 25. The composition of Claim 24 wherein said peptide is present in an amount effective to inhibit growth of a target cell. 26. A process for inhibiting growth of a target cell, virus, or virally-infected cell, comprising: administering a biologically active amphiphilic peptide, said peptide including the following basic structure X- 4 : R-,-R 2 -R 2 -R 3 -R 4 -R 2 -R 2 -R,-R 2 -R 2 -R 2 -R 4 -R 2 -R 2 -, wherein R- is a basic hydrophilic amino acid, R 2 is a hydrophobic amino acid, R- is a neutral hydrophilic or hydrophobic amino acid, and R 4 is a basic hydrophilic or hydrophobic amino acid. 27. The process of Claim 26 wherein the peptide includes the following structure: Y 14 -X 14 , wherein X, 4 is the basic peptide structure of Claim 29, and Y- 4 is: (i) R 2 ; (ii) R 2 -R 2 ; (iii) R 4 -R 2 -R 2 ; (iv) R 3 -R 4 -R 2 -R 2 ; (v) R 2 -R 3 -R 4 -R 2 -R 2 ; ( vi ) R 2 - 2 - 3- 4 - 2 -R 2 ; or (vii) R 1 -R 2 -R 2 -R 3 -R 4 -R 2 -R 2 - 28. The process of Claim 26 wherein the peptide includes the following structure: X 14" 2 14' whβrein x i4 is the b asic peptide structure of Claim 29, and Z- 4 is: (i) R χ ; (iii) R 1 -R 2 -R 2 ; (iv) R r R 2 -R 2 -R 3 ; (V) R r R 2 -R 2 -R 3 -R 4 ; (Vi) R 1 -R 2 -R 2 -R 3 -R 4 -R 2 ; or (Vii) R 1 -R 2 -R 2 -R 3 -R 4 -R 2 -R 2 . 29. The process of Claim 26 wherein the peptide includes the following basic structure: ( γ 14 )a-X 14 -(Z 14 )b, wherein Y χ4 and Z 14 are as previously defined in Claims 27 and 28, and a is 0 or 1, and b is 0 or 1. 30. The process of Claim 29 wherein said peptide has the following structural formula Lys Leu Ala Ser Lys Ala Gly Lys He Ala Gly Lys 5 10 He Ala Lys Val Ala Leu Lys Ala Leu - NH_ 15 20 31. The peptide of Claim 29 wherein said peptide has the following structural formula: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Orn He Ala Lys He Ala Gly Lys He 15 20 Ala - NH 2 32. The process of Claim 26 wherein said administering is to an animal host in an effective anti-tumor amount. 33. The process of Claim 26 wherein said administering is to an animal host in an effective anti-viral amount. 34. The process of Claim 26 wherein said administering is to an animal host in an effective anti-microbial amount. 35. The process of Claim 26 wherein said administering is to an animal host, in an effective anti-parasitic amount. 36. The process of Claim 26 wherein said administering is to an animal host in an effective antibiotic amount. 37. The process of Claim 26 wherein said administering is to an animal host in an effective anti-spermicidal amount. 38. The process of Claim 26 wherein said administering is to an animal host in an amount effective in treating a wound in said animal host. 39. The peptide of Claim 1 wherein each amino acid resi d u is a D-amino acid residue " or glycine. 40. The peptide of Claim 18 wherein each amino acid resid is a D-amino acid residue or glycine. 41. A biologically active amphiphilic peptide including t following structural formula: (Lys He Ala Lys Lys He Ala) , wherein n is from 2 to 5. 42. The peptide of Claim 41 wherein said peptide has the following structural formula: (Lys He Ala Lys Lys He AlaJ.-NH-. 43. A process for inhibiting growth of a target cell, virus, or virally-infected cell, comprising: administering to a host the biologically active amphiphilic peptide of Claim 41, said peptide being administere in an amount effective in inhibiting growth of a target cell, virus, or virally-infected cell in a host. 44. The process of Claim 43 wherein said administering is to an animal host is an effective anti-tumor amount. 45. The process of Claim 43 wherein said administering is to an animal host in an effective anti-viral amount. 46. The process of Claim 43 wherein said administering is to an animal host in an effective anti-microbial amount. 47. The process of Claim 43 wherein said administering is to an animal host in an effective anti-parasitic amount. 48. The process of Claim 43 wherein said administering is to an animal host in an effective antibiotic amount. 49. The process of Claim 43 wherein said administering is to an animal host in an effective anti-spermicidal amount. 50. The process of Claim 43 wherein said administering is to an animal host in an amount effective in treating or healin g wound in said animal host. 51. A biologically active amphiphilic peptide selected fr the group consisting of: (SEQ ID NO:61)-NH 2 (SEQ ID NO:62)-NH 2 (SEQ ID NO:63)-NH 2 ; and (SEQ ID NO:64)-NH 2 . 52. A process for inhibiting growth of a target cell, virus, or virally-infected cell, comprising: administering a biologically active amphiphilic peptide, said peptide selected from the group consisting of: (SEQ ID NO:61)-NH 2 (SEQ ID NO:62)-NH 2 (SEQ ID NO:63)-NH 2 ; and (SEQ ID NO:64)-NH 2 . SUBSTITUTE SHEET

Inventors: BERKOWITZ BARRY, KARI U PRASAD, MALOY W LEE, BERKOWITZ, BARRY, KARI, U., PRASAD, MALOY, W., LEE
Applicants: MAGAININ SCIENCES INC, MAGAININ SCIENCES INC.
Application year: 1991
Main classification: C07K7
IPC codes: A61K38, A61P31, A61P35, C07K7, C07K14