COMPOSITION AND TREATMENT WITH BIOLOGICALLY ACTIVE PEPTIDES HAVING C-TERMINAL SUBSTITUTIONS

Abstract: A C-terminal substituted peptide or protein of formula (I), wherein X is a biologically active amphiphilic ion channel-forming peptide or protein. T is selected from the group consisting of: (a) O-R, wherein R is a substituted or unsubstituted aliphatic, aromatic or aralkyl group having from 1 to 10 carbon atoms; (b) NH-NH2; (c) NH-OH; and (d) alpha , wherein R' and R" are hydrogen or selected from the class consisting of group (i) and group (ii), wherein group (i) is a hydroxy-substituted aliphatic, aromatic or aralkyl group having no more than 10 carbon atoms, and group (ii) is an amino-substituted aliphatic, aromatic, aralkyl, or alkylaromatic group, preferably having no more than 10 carbon atoms, and at least one of R' and R" is group (i) or group (ii).

Description: ≠ COMPOSITION AND TREATMENT WITH BIOLOGICALLY ACTIVE PEPTIDES HAVING C-TERMINAL SUBSTITUTIONS This application is a continuation-in-part of application Serial No . 713 , 716 , filed June 12 , 1991 . This invention relates to biologically active peptides and proteins , and more particularly to compositions rind uses involving biological ly active peptides having C- terminal substitutions . In accordance with an aspect of the present invention, there is provided a composition comprising a C-terminε] substituted peptide or protein of the formula : O wherein X is a biologically active amphiphiiic peptide or protein. The peptide or protein is an ion channel-forming peptide or protein. T is selected from the group consisting of: (a) OR, wherein R is a substituted or unsubstituted aliphatic, aromatic, or aralkyl group having from 1 to 10 carbon atoms. Preferably, R is an alkyl group. (The resulting C-terminal substituted peptide is sometimes hereinafter referred to as a C-terminal ester.); (b) NH-NH-, (The resulting C-terminal substituted peptide is sometimes referred to as a C-terminal hydrazide.); SUBSTITUTE SHEET (c) NH-OH (The resulting C-terminal substituted peptide is sometimes hereinafter referred to as a C-terminal hydroxylamine. ); , wherein R' and R" are hydrogen or selected from the class consisting of group (i) and .group (ii), wherein; group (i) is a hydroxy-substituted aliphatic, aromatic, or aralkyl group having no more than 10 carbon atoms. Preferably, group (i) is a hydroxy-substituted alkyl group. Most preferably, group (i) is CH-CH-OH. Group (ii) is an amino-substituted aliphatic or aromatic, aralkyl, or alkylaromatic group. Preferably the amino-substituted group has no more than 10 carbon atoms. Preferably, group (ii) is an amino-substituted alkyl group. Most preferably, group (ii) is CH-CH-NH,. The peptides terminated with group (d) are sometimes hereinafter referred to as substituted C-terminal amides. As hereinabove stated, the peptide or protein is an ion channel-forming peptide or protein. An ion channel-forming peptide or protein or ionophore is a peptide or protein which increases the permeability for ions across a natural or synthetic lipid membrane. B. Christensen et al. PNAS Vol. 85 Pgs. 5072-76 (July, 1988) describes methodology which indicates whether or not a peptide or protein has ion channel-forming properties and is therefore an ionophore. As used herein an ion channel-forming peptide or ion channel forming protei is a peptide or protein which has ion channel-forming properties as determined by the method of Christensen et al. An a phiphilic peptide is a peptide which includes both hydrophobic and hydrophilic peptide regions. Applicants have found that, when the C-terminal of the biologically active peptides is substituted with one of the groups hereinabove described, such peptides have increased SUBSTITUTESHEET biological activity as compared with peptides having unsubstituted C-terminals. The ion channel-forming peptides employed in the present invention are generally water soluble to a concentration of at least 20 mg/ml at neutral pH in water. In addition, the structure of such peptide provides for flexibility of the peptide molecule. Such peptides are capable of forming an alpha-helical s assume an amphiphilic structure. When the peptide encounters an oily surface or membrane, the peptide chain folds upon itself into a rod-like structure. In general, such peptides have at least 7 amino acids, and preferably at least 20 amino acids. In most cases, such peptides do not have in excess of 40 amino acids. In general, the peptide or protein is administered topically at a concentration of from .05% to 10%. When administered systemically, the peptide or protein is employed to provide peptide or protein dosages of from l g to 500mg per kilogram of host weight. The compositions 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. Thus, for example, the compositions 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. SUBSTITUTESHEET 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 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 peptide 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 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 microbial 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 systemic lly and may be in any suitable SUBSTITUTESHEET 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, protein inhibitors, or compatible drugs where such a combination is seen to be desirable or advantageous in controlling infection caused by harmful microorganisms including protozoa and the like, as well as by parasites and viruses. 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 antispermicidal 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 to reverse the inhibition of wound healing caused by a depressed or compromised immune system. The compositions of the present invention may also be used in the treatment of external burns and to treat and/or prevent skin and burn infections. In particular, the compositions may be SUBSTITUTE SHEET used to treat skin and burn infections caused by organisms such as, but not limited to, P. eruginosa and S.aureus. The peptides of the present invention may be used in the treatment of external burns and to treat and/or prevent skin and burn infections. In particular, the peptides may be used to treat skin and burn infections cause by organisms such as, but not limited to, P. aeruginosa 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. aeruginosa, S. aureus, and N. gonorrhoeae, by fungi such as but not limited to C. albicans and A. fumigatus, 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. fumigatus, which forms spores as well. The peptides may also be administered to plants in order to prevent, inhibit, or destroy the growth of microbes, bacteria, fungi, viruses, cysts, spores, or parasites in plants. In accordance with one embodiment, each of the amino acid residues of the peptide or protein 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 peptide or protein, when consisting entirely of D-amino acid or glycine residues, may have increased resistance to proteolytic enzymes while retaining their biological activity. Such peptides or proteins thus may be administered orally. Also, in accordance with another embodiment, all of the amino acid residues are D-amino acid or glycine residues, or -amino acid or glycine residues. In accordance with a preferred embodiment, the peptide is a basic (positively charged) polypeptide having at least sixteen SUBSTITUTESHEET amino acids wherein the polypeptide includes at least eight hydrophobic amino acids and at least eight hydrophilic amino acids. Still more particularly, the hydrophobic amino acids are in groups of two adjacent amino acids, and each group of two hydrophobic amino acids is spaced from another group of two hydrophobic amino acids by at least one amino acid other than a hydrophobic amino acid (preferably at least., two amino acids) and generally by no greater than four amino acids, and the amino acids between pairs of hydrophobic amino acids may or may not be hydrophilic. The hydrophilic amino acids are generally also in groups of two adjacent amino acids in which at least one of the two amino acids is a basic hydrophilic amino acid, with such groups of two hydrophilic amino acids being spaced from each other by at least one amino acid other than a hydrophilic amino acid (preferably at least two amino acids) and generally no greater than four amino acids, and the amino acids between pairs of hydrophilic amino acids may or may not be hydrophobic. In accordance with a particularly preferred embodiment, the polypeptide comprises a chain of at least four groups of amino acids, with each group consisting of four amino acids. Two of the four amino acids in each group are hydrophobic amino acids, and two of the four amino acids in each group are hydrophilic, with at least one of the hydrophilic amino acids in each group being a basic hydrophilic amino acid and the other being a basic or neutral hydrophilic amino acid. The hydrophobic amino acids may be selected from the class consisting of Ala, Cys, Phe, Gly, lie, Leu, Met, Pro, Val, Trp, Tyr, norleucine (Nle), norvaline (Nva), and Cyclohexylalanine (Cha). The neutral hydrophilic amino acids may be selected from the class consisting of Asn, Gin, Ser, and Thr and homoserine (Hse). The basic hydrophilic amino acids may be selected from the class consisting of Lys, Arg, His, Orn, homoarginine (Har), 2, 4 - diaminobutyric acid (Dbu), and p-aminophenylalanine. SUBSTITUTESHEET Each of the groups of four amino acids may be of the sequence ABCD, BCDA, CDAB, or DABC, wherein A and B are each hydrophobic amino acids and may be the same or different, one o C or D is a basic hydrophilic amino acid, and the other of C or is a basic or neutral hydrophilic amino acid and may be the same or different. In a preferred embodiment, the polypeptide chain may comprise 5 or 6 groups of this sequence. In each group, eac of A, B, C and D may be the same in some or all of the groups or may be different in some or all of the groups. The polypeptide chain preferably has at least 20 amino acids, and no greater than 50 amino acids. It is to be understood, however, that the polypeptide does not have to consist entirely of the groups described above. The polypeptide may have amino acids extending from either or both ends of the noted ςrroups forming the polypeptide chain and/or there may be amino acids between one or more of the at least four groups and still remain within the scope of the invention. The groups of amino acids may be repeating groups of amino acids, or the amino acids in the various groups may vary provide that in each group of the at least four groups of amino acids there are two hydrophobic and two hydrophilic amino acids as hereinabove noted. Thus, in a preferred embodiment, the biologically active polypeptide comprises a chain including at least four groups of amino acids, each containing four amino acids. Two of the four amino acids in each group are hydrophobic, at least one amino acid is basic hydrophilic, and the remaining one is basic or neutral hydrophilic, with the polypeptide chain preferably havin at least 20 amino acids but no greater than 50 amino acids. In one embodiment, each of the at least four groups of amino acids which are in the peptide chain is of the sequence A-B-C-D, B-C-D-A, C-D-A-B or D-A-B-C wherein A and B are hydrophobic amino acids, one of C or D is a basic hydrophilic amino acid, and the other of C or D is basic or neutral hydrophilic amino acid. SUBSTITUTESHEET The resulting polypeptide chain, therefore, may have one of the following sequences: (X 1 ) a (A-B-C-D) n (Y 1 ) b ( X 2 ) a (B-C-D-A) n (Y 2 ) b (X 4 ) a (D-A-B-C) n( Y 4 ) b wherein X- ^ is D; C-D- or B-C-D-, Y., is -A or -A-B or -A-B-C X- is A-, D-A- or C-D-A- Y- is -B, -B-C or B-C-D X-is B-, A-B-, D-A-B- Y- is -C, -C-D, -C-D-A X 4 is C-, B-C-, A-B-C- Y 4 is -D, -D-A, -D-A-B a is 0 or 1; b is 0 or 1 and n is at least 4. It is to be understood that the peptide chain may include amino acids between the hereinabove noted groups of four amino acids provided that the spacing between such groups and the charge on the amino acids does not change the characteristics of the peptide chain which provide amphiphilicity and a positive charge and do not adversely affect the folding characteristics of the chain to that which is significantly different from one in which the hereinabove noted group of four amino acids are not spaced from each other. As representative examples of peptides in accordance with the present invention, there may be mentioned. I Ala-Phe-Ser-Lys-Ala-Phe-Ser-Lys-Ala-Phe-Ser- Lys-Ala-Phe-Ser-Lys-Ala-Phe-Ser-Lys (SEQ ID NO:l) II Ala-Phe-Ser-Lys-Ala-Phe-Ser-Lys-Ala-Phe-Ser- Lys-Ala-Phe-Ser-Lys-Ala-Phe-Ser-Lys-Ala-Phe- Ser-Lys. (SEQ ID NO:2) III Phe-Ser-Lys-Ala-Phe-Ser- Lys-Ala-Phe-Ser-Lys-Ala- (SEQ ID NO:3) Phe-Ser-Lys p -Ala- SUBSTITUTE SHEET IV Ser-Lys-Ala-Phe-Ser-Lys-Ala- Phe-Ser-Lys-Ala-Phe-Ser-Lys-Ala- (SEQ ID NO : 4) Phe-Ser-Lys-Ala-Phe- V Lys-Ala-Phe-Ser-Lys-Ala-Phe-Ser-Lys-Ala-Phe-Ser- Lys-Ala-Phe-Ser (SEQ ID NO:5) The peptide, may have amino acids extending from either end of the chain. For example, the chains may have a Ser-Lys sequence before the "Ala" end, and/or an Ala-Phe sequence after the "Lys" end. Other amino acid sequences may also be attached to the "Ala" and/or the "lys" end. Similarly, in any polypeptide chain having at least four groups of amino acids of the sequence as described above, the chain may have, for example, a C-D sequence before the first A-B-C-D group. Also other amino acid sequences may be attached to the "A" and/or the "D" end of one of these polypeptide chains. Also there may be amino acids in the chain which space one or more groups of the hereinabove noted four amino acids from each other. The peptides with the substituted C-terminals may be synthesized by either solid phase peptide synthesis or solution methods of peptide synthesis. When solid phase peptide synthesis is employed, the peptide, with appropriate side chain protection, is synthesized by established methods on a suitable resin. The protected peptide resin is suspended in methanol (25 ml/g of resin) and stirred with a large excess of an appropriate amino component for several days in order to produce a C-terminal substituted hydrazide, hydroxylamine, or amide having one of the structures hereinabove described. When a diamino compound is used, one of the amino groups is suitably protected. The peptide plus resin is filtered, washed with methanol, and dried. The resin and peptide mixture is subjected to HE treatment and the deprotected peptide amide, hydroxylamine, or hydrazide is extracted with dilute acetic acid and lyophilized. SUBSTITUTESHEET The C-terminal esters can be obtained by transesterification of the peptide with an appropriate alcohol as solvent in the presence of a tertiary base such as triethylamine. The work up and the isolation of the peptide ester is similar to the procedure for isolating the other C-terminal substituted peptides. When the synthesis is carried out by standard solution methods of peptide synthesis, the C-terminal substituted ester peptide may be made by beginning the solution synthesis with an appropriate amino acid ester. If other modified C-terminal • peptides are desired, the protected peptide C-terminal ester may be reacted with hydroxylamine or hydrazine to produce an appropriate peptide C-terminal hydroxylamine or peptide C-terminal hydrazide, respectively. If a peptide C-terminal substituted amide is desired, the C-terminal ester is hydrolyzed by standard techniques, and the protected peptide acid is reacted with the desired amino component (suitably protected) by standard coupling procedures. The protected peptide derivative is then deprotected and purified. It is also possible to produce the peptides in unsubstituted form by genetic engineering techniques. The codons encoding the amino acids of the peptides are known to those skilled in the art, and thus one may construct DNA encoding any of the peptides by accepted techniques, and clone such DNA into an expression vehicle such as, for example, a plasmid, and transfect such an expression vehicle into a cell which will express the peptides. Upon expression of such peptide, the peptide may be substituted at the C-terminal in accordance with the present invention by techniques such as those hereinabove described. In accordance with another preferred embodiment, the peptide may be a magainin peptide. A magainin peptide is either a magainin such as magainin I, II or III or an'analogue or derivative thereof. The magainin SUBSTITUTE SHEET peptides preferably include the following basic peptide structure "" R ll "R ll "R 12 "R 13 ' ,R ll "R 14 "R 12 "R ll " R 14 "R 12 'R ll "R ll~ R ll "R 14a "{R 15 ) n "R 14a "R 14 "" wherein R-- is a hydrophobic amino acid, R_- is a basic hydrophilic amino acid; R,-, is a hydrophobic, neutral hydrophilic, or basic hydrophilic amino acid; R.. and R_ . are hydrophobic or basic hydrophilic amino acids; R._ is glutamic acid or aspartic acid, or a hydrophobic or a basic hydrophilic amino acid, and n is 0 or 1. In a preferred embodiment, R__ is a hydrophobic or neutral hydrophilic amino acid, R- . is a hydrophobic amino acid, and R.-. is glutamic acid or aspartic acid. Thus, for example, a magainin peptide may include the following structure: "Y 12 "X 12 " where X.,, is the hereinabove described basic peptide structure and Y__. is ( i ) *i2 where Rηη/ R i2' R i4 ancl R l4a are as P reviousi y defined. A magainin peptide may also have the following structure: ~ X 12 "Z 12 " wherein 12 is as previously defined and Z- is: (i) R. fi where R, g is a basic hydrophilic amino acid or asparagine or glutamine. (ii) R 16 -R 17 where R.-, is a neutral hydrophilic amino acid, a hydrophobic amino acid, or a basic hydrophilic amino acid. Preferably, R-- is a neutral hydrophilic amino acid. A magainin peptide may also have the following structure: < Y 12>a- Xl2"(Zl2) b SUBSTITUTESHEET where X-,,, ^i? anc * Z 12 are s P reviouslv defined and a is 0 or 1 and b is 0 or 1. The magainin peptides may also include the following basic peptide structure X--: ""R 14 "R ll "R 14a "R 12 "R ll "R ll "R 12 "R 13 " R n -R 14 -R 12 -R -R n -R 12 -, wherein ι R 12 ,R 13 R χ4 , and R χ4& are amino acids as hereinabove described. The magainin peptide may also include the following structure X._-2- 3 ; wherein X__ is the hereinabove described basic peptide structure and Z.- is (R ll ) n-< R ll>n-< R ll)n^ R 14a)n-< R 15)n-< R 14a)n^ R 14 ) n-< R 16)n-< R 17)n wherein R^, R nΛ R i a ' R 15* R 16' and R 17 are as nereinaDove described, and n is 0 or 1, and each n may be the same or different. The magainin peptides generally include at least fourteen amino acids and may include up to forty amino acids. A magainin peptide preferably has 22 or 23 amino acids. Accordingly, the hereinabove described basic peptide structures of a magainin peptide may include additional amino acids at the amino end or at the carboxyl end, or at both ends. As representative examples of such magainin peptides, there may be mentioned peptides having the following primary sequences as given in the accompanying sequence listing as well as appropriate analogues and derivatives thereof: (a) (SEQ ID N0:6) (Magainin I) (b) (SEQ ID N0:7) (Magainin II) (c) (SEQ ID N0:8) (Magainin III) The following are examples of peptide derivatives or analogs of the basic structure: (d) (SEQ ID N0:9) (e) (SEQ ID NO:10) SUBSTITUTE SHEET ( f ) ( SEQ ID NO : 11 ) Magainin peptides are described in Proc. Natl. Acad Sci. Vol. 84 pp. 5449-53 (Aug. 87). The term "magainin peptides" as used herein refers to the basic magainin structure as well as derivatives and analogs thereof, including but not limited to the representative derivatives or analogs. In accordance with a further embodiment, the peptide may be a PGLa peptide or an XPF peptide. A PGLa peptide is either PGLa or an analogue or derivative thereof. The PGLa peptides preferably include the following basic peptide structure 14 * - 11 - R 17 - R 12 - R ιι- R i4- R i "R ll~ R ll "R 14 "R 12 "R ll "R ll "R 12 "R ll~ R ll "R ll "R 12 " where R-,-,/ R i2' R 14 anc * R 17 are as P rev i° us ly defined. The PGLa peptides generally include at least seventeen amino acids and may include as many as forty amino acids. Accordingly, the hereinabove described basic peptide structure for a PGLa peptide may include additional amino acids at the amino end or at the carboxyl end or at both the amino and carboxyl end. Thus, for example, a PGLa peptide may have the following structure: ~ Y 14~ X 14~ where X_. is as previously defined and Y 14 is (i) ; (ii) R 14 -R n where R lχ and R- 4 are as previously defined. For example, a PGLa peptide may also have the following structure: "X 14 "Z 14~ where X- . is as previously defined; and Z- 4 is : (i ) R 11 ? or (ii ) Rll - Rll SUBSTITUTE SHEET where R., is as previously defined. A PGLa peptide may also have the following structure: < Y 14>a "Xl4"(Zl4) b where X 14 ; Y 14 and ∑ 14 are as previously defined, a is 0 or 1 and b is 0 or 1. An XPF peptide is either XPF or an analogue or derivative thereof. The XPF peptides preferably include the following basic peptide structure X lg * —R 11 -R 17 -R 12 -R 11 -R 14 -R 18 -R 17 - R 11 "R 14 'R 12 "R 11 "R 11 "R 12 " R ιι _R ιr wherein R ll' R 12' R 14' R 15 and R 17 are as P reviousl y defined and R ιa is glutamine or asparagine or a basic hydrophilic, or hydrophobic amino acid and, n is 0 or 1. The XPF peptides generally include at least nineteen amino acids and may include up to forty amino acids. Accordingly, the hereinabove described basic peptide structure of XPF may include additional amino acids at the amino end, or at the carboxyl end or at both the amino and carboxyl ends. Thus, for example, an XPF peptide may include the following structure: "Y 16 "X 16 " where X lg is as previously defined and Y lg is (i) R or (ϋ) R i4- R ιι where R-. and R- 4 are as previously defined. An XPF peptide may include the following structure: "X 16 "Z 16 " where X- g is as previously defined and Z. g is (i) R n ; or (iii) R- 1 -R 18 -Proline; or (iv) R-^-R-^-Proline-R-^ SUBSTITUTE SHEET _ lg _ An XPF peptide may also have the following structure: •γ i6>a "Xl6<2l6) b where lg / Y 16 and Z lg are as previously defined: a is 0 or 1 and b is 0 or 1. Preferred are XPF or PGLa peptides, which are characterized by the following primary amino acid sequences as given in the accompanying sequence listing: PGLa : (SEQ ID NO:12) XPF : (SEQ ID NO:13) 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. In accordance with yet another embodiment, the peptide may be a CPF peptide or appropriate analogue or derviative thereof. CPF peptides as well as analogues and derivatives thereof are herein sometimes referred to collectively as CPF peptides. The CPF peptide may be one which includes the following basic peptide structure 2 : "*R 2l "R 21~ R 22~ R 22 "R 2l "R 2l "R 23 "R 2l " ~ R 2l "R 21~ R 23~ R 2l "R 2l "R 24~ R 25 "R 2l " wherein R,. is a hydrophobic amino acid; R 77 is a hydrophobic amino acid or a basic hydrophilic amino acid; R, 3 is a basic hydrophilic amino acid; R_. is a hydrophobic or neutral hydrophilic amino acid; and R ?t - is a basic or neutral hydrophilic amino acid. The hereinabove basic structure is hereinafter symbolically indicated as 2 π- The hydrophobic amino acids are Ala, Cys, Phe, Gly, lie, Leu, Met, Val, Trp, Tyr, norleucine (Nle), norvaiine (Nval), and cyclohexylalanine (Cha). SUBSTITUTESHEET The neutral hydrophilic amino acids are Asn, Gin, Ser, and Thr. The basic hydrophilic amino acids are Lys, Arg, His, Orn, homoarginine (Har), 2, 4-diaminobutyric acid (Dbu), and p-aminophenylalanine. The CPF peptide may include only the hereinabove noted amino acids or may include additional amino acids at the amino and/or carboxyl end or both the amino and carboxyl end. In general, the peptide does not include more than 40 amino acids. The CPF peptides including the above basic structure preferably have from 1 to 4 additional amino acids at the amino end. Accordingly, such preferred peptides may be represented by the structural formula: Y 20 " X 20 wherein X--. is the hereinabove described basic peptide structure and Y,_ is (i) R 25 -, or ( ii ) 22" R 25 _; or ( iii ) R 21- R 22" R 25 ; or ( iv ) R 22" R 21" R 22" R 25 ; Preferably Glycine - R 21 - 22 - R 25 . wherein R 2 n/ R 22 and R 25 are as P reviousl y defined. The carboxyl end of the basic peptide structure may also have additional amino acids which may range from 1 to 13 additional amino acids. In a preferred embodiment, the basic structure may have from 1 to 7 additional amino acids at the carboxyl end, which may be represented as follows: " X 20 " Z 20 wherein X is the hereinabove defined basic peptide structure and Z 20 is (i) R 21 - , or (ϋ ) R 21- R 21- ; or SUBSTITUTE SHEET (iii ) R 2 ι- 2i- R 2 ; ° r (iv) R 2 ι- R 2 R 24- R 24 ; or (v) R 21- R 2 R 24 'R 24- R 26 ; or (vi ) R 2 l- R 21- R 24- R 24- R 26 "Gln; or (vii) R 21 -R 2 --R 24 -R 24 -R 2g -Gln-Gln, wherein R 21 and R 24 are as previously defined, and R_, g is proline or a hydrophobic amino acid. Preferred peptides may be represented by the following structural formula Y 20 a " X 20 " (Z 20 ) b wherein X 2 n' Y 20 nd Z 2 0 are as P rev i° usl y define d and a is 0 or 1 and b is 0 or 1. Representative examples of CPF peptides which may be employed, some of which have been described in the literature, include the following sequences as given in the accompanying sequence listing: (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 N0:21) (SEQ ID NO:22) (SEQ ID N0:23) (SEQ ID NO:24) (SEQ ID NO:25) (SEQ ID NO:26) The above is expressed as single letter code for amino acids. SUBSTITUTESHEET 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 Acids Research 13, 1817-1828; Gibson, B.W. , Poulter, L. , Williams, D.H. , and Maggio, J.E. (1986) J. Biol. Chem 261, 5341-5349. In accordance with yet another embodiment, the peptide may include one of the following basic structures X 3 - through X 3 _ wherein X 31 is -[R 31 -R 32 -R 32 -R 33 -R 31 -R 32 -R 32 n 32 is " - R 32 "R 32~ R 33 "R 3l "R 32 "R 32 "R 31 " n 33 is " - R 32 "R 33 -R 3l "R 32 "'R 32 "R 3l "R 32 " n X 34 is ~- R 33~ R 31~ R 32~ R 32~ R 31~ R 32~ R 32 " n : 35 is -[ 3 1 - R 32 - 3 2 - R 3 1 - R 3 2 - R 3 2 - 33 " n X 36 is ~ [R 32~ R 32~ R 3l "R 32~ R 32~ R 33~ R 31 " n and X '3.7 is "[R 32 "R 3l "R 32 "R 32 "R 33 "R 3l "R 32 " n wherein R 31 is a basic hydrophilic amino acid, R,_, IS a hydrophobic amino acid, R 33 is a neutral hydrophilic or hydrophobic amino acid, and n is from 2 to 5. The basic hydrophilic amino acids may be selected from the class consisting of Lys, Arg, His, Orn, homoarginine (Har), 2, 4-diaminobutyric acid (Dbu), and p-aminophenylalanine. The hydrophobic amino acids may be selected from the class consisting of Ala, Cys, Phe, Gly, lie, Leu, Met, Val, Trp and Tyr,norleucine (Nle), norvaiine (Nva), and cyclohexylalanine (Cha). The neutral hydrophilic amino acids may be selected from the class consisting of Asn, Gin, Ser and Thr. In accordance with one embodiment, when the peptide includes the structure 31 the peptide may include the following structure: Y 3l "X 31' wherein X-,. is as hereinabove described, and Y... IS: (i) Λ 32' (ϋ) κ 32 *32' SUBSTITUTE SHEET (V) R 32- R 33- R 31- R 32 "R 32 ; ° r ( i ) R 3 2 - R 32~ R 33- R 3r R 32- R 32' wherein R 3i ' R 3 ' and R 33 are as hereinabove described In accordance with another embodiment, when the peptide includes the structure 31 / the peptide may include the following structure: X 31 ~ 31 ' wnere i n 31 i s as hereinabove described, and Z__ is: (i) R 31 ; (ii) R 31 - 32 ; (iii) R 31 -R 32 -R 32 ; (iv) 31 - 3 2 - R 3 2 - 3 3 (v) 31 - 3 2 - 3 2 - R 33- 3 or (vi ) R 3 1 - R 32 _R 32 "R 33 "R 3l "R 32' In accordance with yet another embodiment, the peptide may include the following structure: (Y 31 ) -X 31 -(Z 31 ), , wherein Y 31 and Z 3 - are as previously defined, a is 0 or 1, and b is 0 or 1. When the peptide includes the structure X 32 / tne peptide may include the following structure: Y 32 " 32 ' wnere n X 3 2 -- s as h ere i nafaove described, and Y 32 IS: (i) R 31' (ii) 32 - 31 ; (iii) R 32" R 32 "R 31 ; (iv) R 31 - R 32 "R 32 "R 31 f ( v ) R 33- R 3r R 32 _R 32- R 31 ; θr (vi) R 32 "R 33 "R 3l "R 32 "R 32 "R 31 • In another embodiment, when the peptide includes the structure X 32r the peptide may include the following structure: X 32 ~ 32 *" wnere i n X 32 -~ s as hereinabove described, and Z 32 s: SUBSTITUTESHEET (i) R 32 ; (ii) R 32 -R 32 ; ( iii ) 32~ R 32" R 33 ; (iv) R 32 "R 32 "R 33 "R 31 ; ( v > R 32- R 32 _R 33- R 3 R 32 ; or ( vi) R 32 "R 32 "R 33 _R 3l "R 32 "R 32' In accordance with yet another embodiment, the peptide may include the following structure: t - Y 32' ) a " X 32 " Z 32* , b' wherein Y 32 and Z 32 re as reviously defined, a is 0 or 1, and b is 0 or 1. In accordance with another embodiment, when the peptide includes the structure 33 . the peptide may include the following structure: Y 33 ~ X 33 wherein 33 is as hereinabove described, and Y__ is: (i) R 32 ; (ii) R 31 - R 32 ; (iii) R 3 2 - R 31 - R 32 '' (iv) R 32 -R 32 -R 31 -R 32 ; < v > R 3r R 32 "R 32- R 3l "R 32 ; 0r (vi) 33- 31 - 3 2 - 3 2 - 3i- R 3 2 ' wherein R^, R 32 , and R 33 are as hereinabove described. In accordance with another embodiment, when the peptide includes the structure X33 / the peptide may include the following structure: 33 ~ Z 33 wherein X 33 is as hereinabove described, and Z 33 IS: (i) R 32 ; (ii) R 32 -R 33 ; (iii) 32 - 33- 31 ; ^ iv) R 32 _R 33 "R 3l "R 32 ; (v > R 32- R 33- R 3 R 32 "R 32 ; ° r (vi ) 3 2 - R 33- R 31 - 3 2 - R 32- R 31- SUBSTITUTE SHEET In accordance with yet another embodiment, the peptide may include the following structure: (Y 33 ) a - 33 - (233) ] -,' wherein Y 33 and Z 33 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 34 . the peptide may include the following structure: Y 34 " X 3 4' wherein X 34 is as hereinabove described, and Y, . is: (i) 32 ; (ϋ) R 32 - R 32 ; (iii) R 31 -R 32 -R 32 ; (iv) R 3 Y2 - R 31 - R 3 2 - R 3 ' (V) R 32~ R 32~ R 31~ R 32~ R 32 ; or (vi) R 31 - 3 2 - 3 2 - R 3 1 - 3 2 - 32' wherein R^, R 32 and R 33 are as hereinabove described. In accordance with another embodiment, when the peptide includes the structure X 34 . the peptide may include the following structure: X 3 4~ Z 3 4' wherein X 34 is as hereinabove described, and Z 34 is: (i) R 33 ; t 11) R 33" R 31 ; (iii ) R 33 - R 31 - R 32 ; (iv) R 33 "R 3l "R 32 "R 32 ; < v > R 33 "R 31 "R 32- R 32- R 31 ; ° r ( i ) R 33- 31 - R 3 2 - R 32- R 31~ R 32- In accordance with yet another embodiment, the peptide may include the following structure: (Y 34 ) a - X 34 - (Z 34 ) b , wherein X 34 and Z 34 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 X35. the peptide may include the following structure: SUBSTITUTESHEET Y 35 ~ X 35 ' wherein X 35 is as hereinabove described, and Y__ 1S: (i) R 33 ; (ii) R 32 -R 33 ; (iii) R 32 -R 32 -R 33 ; ( iv ) R 31 - R 3 2 - R 3 - 3 3 ; < v > R 32 "R 3 R 32- R 32- R 33 ; θr (vi) R 32 -R 32 -R 31 -R 32 -R 32 -R 33 , wherein R 3χ , R 32 , and R 33 are as hereinabove described. In accordance with another embodiment, when the peptide includes the structure X 35 . the peptide may include the following structure: X 3 5 ~ Z 35 wherein X 35 is as hereinabove described, and Z__. IS: (i) 31 ; (ii) R 31 - R 32 ; (iii) R 31 - R 32 - 32 ; (iv) R 3 1 - R 32 - R 32~ R 3--/ (v) R 31 -R 32 -R 32 -R 31 -R 32 ; or (vi) R 31 -R 32 -R 32 -R 31 -R 32 -R 32 . In accordance with yet another embodiment, the peptide may include the following structure: (Y 35 ) - X 3 -. ( z 3e ) b / wherein X 3 -. and Z 35 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 3g . the peptide may include the following structure: Y3,6, - X3,6.. wherein X3-6- is as hereinabove described, and Y3,6, I S : (v) R 31~ K 32 "R 32 "R 33 ~ R 31 ' or SUBSTITUTE SHEET (vi) R 32 - 31 - R 3 2 - 3 2 - 33- 3 wherein R 3 __, R 32 , and R 33 are as hereinabove described. In accordance with another embodiment, when the peptide includes the structure X 3g / the peptide may include the following structure: X 36 ~ Z 36 ' wherein X 3g is as hereinabove described, and Z_ g is: (i) R 32 ; (ii) 32 - 32 ; (iii) R 32 - R 32 - R 3i' (iv) R 32 -R 32 -R 31 -R 32 ; < v > R 32- R 32 "R 31- R 32- R 32 ; or (vi > R 32~ R 32~ R 3l "R 32~ R 32~ R 33' In accordance with yet another embodiment, the peptide may include the following structure: Y 36>a" X 36 ^36^' wherein Y 36 and Z 36 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 37 . the peptide may includes the structure Y 37 -X 37 , wherein X 37 is as hereinabove described, and Y 37 is: (i) R 32 ; (ii) 31 - 32 ; (iii) 33 - 31 - 32 ; (iv) R 32 "R 33 "R 31~ R 32 ; (v > R 32 "R 32- R 33- R 31- R 32 ; ° r (vi) 3- L - 3 2 - 32 - 33- 3 1 - R 3 2 ' wherein R 31 , R 32 , and R 3 - are as hereinabove described. In accordance with a further embodiment, when the peptide includes the structure X 37 . the peptide may include the following structure: X 37 - Z 37 wherein X 37 is as hereinabove described, and Z 37 is: (i) Λ 32' (ϋ) R 32 " ^31 ; SUBSTITUTESHEET ( iii ) R 32 -R 31 -R 32 ; ( iv) R 32 - R 3 1 - R 3 2 - R 3 2 ; < v ) R 32 "R 3 l "R 32 -R 32 "R 33 ; or (vi ) R 3 2 - R 31 - R 3 2 - R 3 2 - R 3 3 - R 3 1 - In accordance with yet another embodiment, the peptide may include the following structure: (Y 37 ) a - X 37 ( Z 37)fc' wherein Y 37 and Z 37 are as previously defined, a is 0 or 1, and b is 0 or 1. In a preferred embodiment, n is 3, and most preferably the peptide has one of the following structures: (Lys He Ala Gly Lys He Ala) 3 (SEQ ID NO:27). (Lys He Ala Lys He Ala Gly) 3 (SEQ ID NO:28). (Lys He Ala Gly Lys He Gly) 3 (SEQ ID NO:29) . (Lys Leu Ala Gly Lys Leu Ala) 3 (SEQ ID N0:30) . (Lys Phe Ala Gly Lys Phe Ala) 3 (SEQ ID NO:31). (Lys Ala Leu Ser Lys Ala Leu). (SEQ ID NO:32) (Lys Leu Leu Lys Ala Leu Gly) 3 (SEQ ID NO:33) (Lys Ala He Gly Lys Ala He) 3 (SEQ ID NO:34) (Gly He Ala Lys He Ala Lys) 3 (SEQ ID NO:35) (Lys He Ala Lys He Phe Gly) 3 (SEQ ID NO:36) (Gly He Ala Arg He Ala Lys) 3 (SEQ ID NO:37) (Lys Phe Ala Arg He Ala Gly) 3 (SEQ ID NO:38) (Gly Phe Ala Lys He Ala Lys) 3 (SEQ ID NO:39) (Lys He Ala Gly Orn He Ala) 3 (SEQ ID NO:40) (Lys He Ala Arg He Ala Gly) 3 (SEQ ID NO:41) (Orn He Ala Gly Lys He Ala) 3 (SEQ ID NO:42) (Gly He Ala Arg He Phe Lys) 3 (SEQ ID NO:43) (Lys Nle Ala Gly Lys Nle Ala) 3 (SEQ ID NO:44) (Lys Nle Ala Gly Lys He Ala) 3 (SEQ ID NO:45) (Lys He Ala Gly Lys Nle Ala) 3 (SEQ ID NO:46) (Lys Nva Ala Gly Lys Nva Ala) 3 (SEQ ID NO:47) (Lys Nva Ala Gly Lys He Ala) 3 (SEQ ID NO:48) (Lys Leu Leu Ser Lys Leu Cly) 3 (SEQ ID NO:49) (Lys Leu Leu Ser Lys Phe Gly) 3 (SEQ ID NO:50) SUBSTITUTE SHEET (Lys He Ala Gly Lys Nva Ala)- (SEQ ID NO:51) (His He Ala Gly His He Ala) 3 (SEQ ID NO:52) (Ala Gly Lys He Ala Lys Ile) 3 (SEQ ID NO: 53) (He Ala Lys He Ala Gly Lys) 3 (SEQ ID NO: 54) (Lys He Ala Gly Arg He Ala) 3 (SEQ ID NO: 55) (Arg He Ala Gly Arg He Ala) 3 (SEQ ID NO:56) (Lys Val Ala Gly Lys He Ala) 3 (SEQ ID , NO: 57) (Lys He Ala Gly Lys Val Ala) 3 (SEQ ID NO: 58) (Ala Lys He Ala Gly Lys Ile) 3 (SEQ ID NO: 59) (Orn He Ala Gly Orn He Ala) 3 (SEQ ID NO: 60) (Lys Phe Ala Gly Lys He Ala) 3 (SEQ ID NO: 61) (Lys He Ala Gly Lys Phe Ala) 3 (SEQ ID NO: 62) (Lys Cha Ala Gly Lys He Ala) 3 (SEQ ID NO: 63) (Lys Nle Ala Lys He Ala Gly) 3 (SEQ ID NO: 64) (Arg He Ala Gly Lys He Ala) 3 (SEQ ID N0:65) (Har He Ala Gly Har He Ala) 3 (SEQ ID NO: 66) (Xaa He Ala Gly Lys He Ala) 3 (SEQ ID NO: 67) (Lys He Ala Gly Xaa He Ala) 3 (SEQ ID NO: 68) (Lys He Ala (Lys He Ala Gly Lys He Ala) 3 (SEQ ID NO:69) In (SEQ ID NO: 67) and (SEQ ID NO: 68), Xaa is p-aminophenylalanine. In accordance with another embodiment, the biologically active amphiphilic peptide which includes the following basic structure X4. rt 0: R 3l "R 32 "R 32~ R 33 "R 34~ R 32 "R 32 "R 3l "R 32 "R 32 "R 32~ R 34 "R 32 "R 32' wherein R 31 , R 32 ' and R 3 3 ar e as hereinabove described, and R 34 is a basic hydrophilic or hydrophobic amino acid. In accordance with one embodiment, the peptide may include the following structure: Y4i n 0- 4i0-. / wherein X4 ΛO 0 is as hereinabove described, and Y4„0 n is: (i) R 32 ; (ii) 32 - R 32 ; (iϋ) R 34 - R 32 - R 32 ; SUBSTITUTESHEET ( iv ) R 33~ R 34 "R 32 _R 32 ; (v ) R 32 "R 33 "R 34 "R 32 "R 32 ; < v ) R 32~ R 32~ R 33 _R 34 "R 32 "R 32' or (vii) R 31 -R 32 -R 32 -R 33 -R 34 -R 32 -R 32 ,wherein R 3χ/ R 32 , R 33 and 34 are as hereinabove described. In accordance with another embodiment, the peptide may include the following structure: X 4θ" Z 40' w erein X 4Q is as hereinabove described and Z 40 is: (i) R 31 ; (ii) R 31 - R 32 ; (iii) R 31 - 32 - 32 ; ( iv ) R 31 - R 32 - R 3 2 - R 33; (v) 31 - 3 2 - 3 2 - 33- R 34 ( vi) R 3 1 - R 3 2 - R 32 - R 3 3 - R 34- R 3 2 ; or (vii) 3 1 - 3 2 -R 32 - R 33- 3 4 - 3 2 - 3 2 , wherein R 31 , R 32 , R 33 , and R_. are as hereinabove described. In accordance with yet another embodiment the peptide may include the following structure: (Y 40 ) a" X 40" (Z 40 ) b / wherein Y 4Q and Z 40 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 given in the accompanying sequence listing: (SEQ ID NO:70) In another preferred embodiment, the peptide has the following structural formula as given in the accompanying sequence listing: (SEQ ID NO:71) In accordance with a further embodiment, the peptide has one of the following structural formulae as given in the accompanying sequence listing: (SEQ ID NO:72) (SEQ ID NO:73) (SEQ ID NO:74) (SEQ ID NO:75) SUBSTITUTE SHEET _ _. -28- (SEQ ID NO:76) (SEQ ID NO:77) (SEQ ID NO:78) (SEQ ID NO:79) (SEQ ID NO:80) (SEQ ID NO:81) (SEQ ID NO:82) (SEQ ID NO:83) (SEQ ID NO:84) (SEQ ID NO:85) (SEQ ID NO-.86) (SEQ ID NO:87) In accordance with another embodiment, the peptide may include 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 (SEQ ID NO:88) In accordance with another embodiment, the peptide may include the following structural formula: -(Lys Phe Ala Lys Lys Phe Ala)- wherein n is from 2 to 5. Preferably, n is 3, and the peptide has the following structural formula: (Lys Phe Ala Lys Lys Phe Ala) 3 (SEQ ID NO:89) In accordance with another embodiment, the peptide may include the following structural formula: -(Lys Phe 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 Phe Ala Lys Lys He Ala) 3 (SEQ ID NO;90). SUBSTITUTESHEET In accordance with another embodiment, the peptide is selected from the group consisting of the following structural formulae as given in the accompanying sequence listing: (SEQ ID NO:91) (SEQ ID NO:92) (SEQ ID NO:93) (SEQ ID NO:94) In accordance with another ambodiment, the peptide includes the following basic structure ςo : R 4l "R 42 "R 42 "R 4l "R 42 "R 42 "R 4l " 4l "R 42 "R 4l "R 41 R 4 - is a hydrophobic amino acid, and R 4 , is a basic hydrophilic or neutral hydrophilic amino acid. In one embodiment, the peptide includes the basic structure Y 50 " 50 wherein X-.-. is as hereinabove described and Y 50 is: ( i) 41 ; (ϋ) R 42 "R 41 ; or (iii) R 42 ~ R 42 ~ R 4 1 ' wherein R 4 - and R 4 , are as hereinabove described. In one embodiment, R 4.1. is leucine. In another embodiment, R is lysine. Representative examples of peptides in accordance with this aspect of the present invention include those having the following structures: (SEQ ID NO:95) (SEQ ID NO:96) (SEQ ID NO:97) (SEQ ID NO:98) In accordance with another embodiment, the peptide includes the following basic structure X= 2 * R 42" R 41~ R 42~ R 42" R 4l" R 41~ R 42 "R 42 "R 41~ R 42~ R 42' wherein R 41 is a hydrophopbic amino acid and R 4 _ is a basic hydrophilic or neutral hydrophilic amino acid. In one embodiment R 41 is leucine. In another embodiment, R 42 is lysine. SUBSTITUTE SHEET In one embodiment, the peptide includes the basic structure Y__ - c2 ' wherein X-.-, is as hereinabove described, and Y g2 is: (i) R 42 ; (ϋ) R 41 - 42 ; ( iii ) 41 "R 41- R 42 ; ( iv ) 42 - R 1- 41- R 42 ; (v) R 42 'R 42 "R 41~ R 4l "R 42- In one emodiment, the peptide may have the following structure; Lys Lys Leu Leu Lys Lys Leu Lys Lys Leu 5 10 Leu Lys Lys Leu Arg Arg 15 (SEQ ID NO:99) In another embodiment, the peptide includes the basic structure X 52 -Z 52 , wherein X-- is as hereinabove described, and (iv ) 41- R 41- R 2 'R 42 ; or ( v) 41- R 41- R 42- R 42- R 41 ; In one embodiment, the peptide may have the following structure: Lys Leu Lys Lys Leu Leu Lys Lys Leu Lys Lys Leu Leu Lys Lys Leu 5 10 15 (SEQ ID NO:100) In another embodiment, the peptide may include the structure: < Y 52 } a " X 52 " < Z 52>b' wherein X 52' Y 52' and Z 52 are S hereinabove described, and a is 0 or 1, and b is 0 or 1. In accordance with another embodiment, the peptide includes the following basic structure ς4 : R 4l" R 42 -R 42 "R 4l "R 4l "R 42 "R 42~ R 4l "R 42 "R 42 "R 4l "R 4l "R 42 "R 42 "R 43' SUBSTITUTESHEET wherein R 4 , and R 42 are as hereinabove described, and R 4 _ is a netural hydrophilic amino acid. In one embodiment, the peptide may have the following structure: (SEQ ID NO:101) In another embodiment, the peptide may have the following structure: (SEQ ID NO:102) In accordance with yet another embodiment, the peptide includes the following basic structure X 5g : R 4 R 2" R r R r R 42- R 42 "R 4r R r R 2" R 42 "R 4' wherein R 41 and R 42 are as hereinabove described, and R 44 is a neutral hydrophilic amino acid or proline. In one embodiment, the peptide may include the following structure Y- g -X-. β , wherein X-. g is the basic peptide structure hereinabove described, and Y-. g is: X 5g -Z 5g , wherein X, g is as hereinabove described, and Z_. g IS: (i) -R 42 ; (ii) ~ R 42~ R 42' (iii) - 42 - R 42 - 41 . ( iv) - R 42 - 42 - 4 ι_ 41 ' (v ) - R 42 "R 42 "R 41- R 41 '"R 42 ; ( vi ) - 42 - 42 - R 41- R 41- R 42- R 42 ; ° r (vii) -R 42 *R 42" R 41- R 4l "R 42 "R 42 "R 41 * SUBSTITUTESHEET In a preferred embodiment, the peptide may have one of the following structures: (SEQ ID NO:103); or (SEQ ID NO:104). In another emodiment, the peptide may have the structure (Y- g ) -X 5 g-(Z-. g ) b , wherein ςg / γ ς g- and z -. g are s hereinabove described, a is 0 or 1, and b is 0 or 1. In accordance with another embodiment, the peptide includes the following basic structure X ςa : R 41~ R 41~ R 42~ R 42~ R 41~ R 42~ R 42~ R 41~ R 41~ R 42~ R 42~ R 41~ R 43' wherein 41 / R 42 and R.- are as hereinabove described. In accordance with another embodiment, the peptide may include the structure Yc g -Xc g ; wherein X_. β is as hereinabove described, and Y-. g is: (V) - 4 r 41 - 42 - R 42- R 41'- ( i ) - R 42- R 41- R 41- R 42- R 42 "R 41 ° r ( vii ) - R 4 2 - R 42" R 41- R 41- R 42- R 42" R 41' wherein R 41 an d R 42 are as hereinabove described. In another embodiment, the peptide includes the structure X- g -Z 58 , wherein X-.„ is as hereinabove described, and Z 58 is: ( iv ) - 41 - R 45 - R 45- R 43 ; (V) - R 41 - R 45- R 45- R 43- R 41' ( vi ) "R 4l "R 45" R 45- R 43 "R 4l " 43 ; ( vii ) - R 4l "R 45" R 45- R 43 "R 4l "R 43 "R 43' (viii) - R 4i- R 4 5 - R 45- R 43- R 4i- R 43- R 43'- R 45 ; or ( ix ) - R 4 Γ 45 - R 45- R 43- R 4Γ R 43- R 43'- R 45- R 43' wherein R 41 and R.- j are as hereinabove described, and R 45 is proline. In one embodiment, the peptide has the following structure: SUBSTITUTESHEET In one embodiment, the peptide may have the structure (Y 58 ) a -X 5Q -(Z 58 ) b , wherein X 5 g. Y 5 g, and Z-.g are as hereinabove described, a is 0 or 1, and b is 0 or 1. In accordance with another embodiment, the peptide includes the following basic structure X g0 ; R 41 -R 4l " 3 "R 42 -R 4l "R 4l ' ^^ "R 4l "R 4l "R 4l "R 42 "R 4l "R 4l "R 42 "R 42 "R 4l " R 1~ R 42 "" R 42 ~ R 4 ~ R 4 1' wherein R 41 , R 42 , and R 43 are as hereinabove described. In one embodiment, the peptide may have the following structure: (SEQ ID NO:106). In another embodiment, the peptide may include the structure X g0 -Zg 0 wherein X g0 is as hereinabove described, and Z g0 is: ( i ) - R 42 - 42 - 4 ι_ 41 ; ( V ) "R 42 "R 42 "R 41- R 41 "R 42 ; ( i) - R 42 - R 42 -R 41- R 41- R 42- R 42 ; or ( vii) - R 42 "R 42 "R 41- R 41 "R 42 "R 42 "R 41' In accordance with yet another embodiment, the peptide has a structure selected from the group consisting of: (a) 4 ι- 42 - R 42~ R 41 "R 42~ R 42 "R 41 ; ( h ) R 41~ R 4l "R 42~ R 42~ R 4l "R 42~ R 42 "R 41 ; ( c ) R 2 - 1 - R 1 - R 42 - R 2 - R 41 - R 42 - R 42 - R 4i ; ( d ) R 42 "R 42 ~ R 4l "R 4l "R 42 "R 42 "R 4l "R 42 "R 42~ R 41 ; and (e) 4 42 - 42 - 4 ι- 4 ι- 42 - 42 - 41 - R 42 - 42 - 4 wherein R 41 and R 4 - are as hereinabove described. In one embodiment, the peptide has the structure (a), and a representative example of such a structure is (SEQ ID NO:107), which is given in the accompanying sequence listing. In another embodiment, the peptide has the structure (b), and a representative example of such a structure is (SEQ ID NO:108), which is given in the accompanying sequence listing. SUBSTITUTE SHEET In another embodiment, the peptide has the structure (c), and a representative example of such a structure is (SEQ ID NO:109) as given the accompanying sequence listing. In yet another embodiment, the peptide has the structure (d), and a representative example of such a structure is (SEQ ID NO:110) as given in the accompanying sequence listing. In a further embodiment, the peptide has the structure (e), and representative examples of such a structure are (SEQ ID NO:111) and (SEQ ID NO:112) as given in the accompanying sequence listing. In accordance with another embodiment, the peptide has the following structural formula: (SEQ ID NO:113). In accordance with yet another embodiment, the peptide may be a cecropin or sarcotoxin. 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 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, SUBSTITUTESHEET cytolysin, or pore-forming protein. Defensins 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. Exp. Med. , 160:695 (1984). The above articles are hereby incorporated by reference. The term ion channel-forming proteins includes the basic structures of the ion channel-forming proteins as well as analogues and derivatives. In accordance with another embodiment, the peptides or proteins of the present invention may be employed in combination with an ion having pharmacological properties for the purposes hereinabove described. An ion having pharmacological properties is one which when introduced into a target cell, virus, or virally-infected cell, inhibits and/or prevents and/or destroys the growth of the target cell, virus, or virally-infected cell. Such an ion having pharmacological properties is one which in the absence of an ion channel forming peptide or protein 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 or protein and ion having pharmacological properties 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 or protein and ion having pharmacological properties. As representative examples of ions having pharmacological properties which may be employed, there may be mentioned fluoride, peroxide, bicarbonate, and silver ions. SUBSTITUTESHEET The peptide or protein and the ion having pharmacological properties, whether 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 or protein, i.e., the amount of ion is effective to reduce the minimum effective concentration of the peptide or protein for inhibiting growth or a target cell, virus, or virally-infected cell. The ion having pharmacological properties, 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 or protein dosages may be within the ranges hereinabove described. It is also to be understood that the peptide or protein and ion may be delivered or administered in different forms; for example, the ion may be administered orally, while the peptide or protein may be administered by IV or IP. As representative examples of administering the peptide or protein and ion for topical or local administration, the peptide or protein could be administered in an amount of up to about 1% weight to weight and the ion delivered in an amount of about 50mM (about 0.1%). Alternatively, the 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 or protein 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 ion, in particular, sodium fluoride, of 10 meq per kilogram. In accordance with another embodiment, the peptides or proteins 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, SUBSTITUTESHEET teichoplanin, aminoglycosides, hydrophobic antibiotics, penicillins, monobactams, or derivatives or analogues thereof. The bacitracins, gramacidin, polymyxin, vancomycin, and teichoplanin, and derivatives and analogues thereof, are a group of polypeptide antibiotics. A preferred bacitracin is bacitracin A. Aminoglycoside antibiotics include tobramycin, kanamycin, amikacin, the gentamicins (e.g., gentamicin C., gentamicin C 7 , gentamicin C J.lEL), netilmicin, 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 (phenoxymethyl penicillin), σxacillin, cloxacillin, dicloxacillin, flucloxacillin, amoxicillin, and amidinocillin. Preferred penicillins which may be employed are benzyl penicillin and ampicillin. A preferred monobactam which may be employed 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, clarithromycin, etc.; 9-N-alkyl derivatives of erythromycin; midecamycin acetate; azithro ycin; 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 τι/ c ι 2 Position of a macrolide ring known as A-62514 (Abbott); AC-7230 (Toyo Jozo); bbYenzoxazinorifamycin; 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 SUBSTITUTESHEET (Abbott); 3-formylrifamycin SV-hydrazones with diazabicycloalkyl 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 or protein and antibiotic may be adminstered by direct administration to a target cell 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 antibiotic 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 or protein dosages may be those as hereinabove described. As representative exmples of administering the peptide or protein and antibiotic for topical or local administration, the peptide or protein could be administered 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. SUBSTITUTE SHEET In accordance with another embodiment, the peptides or proteins 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 or proteins 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, ofloxacin, enoxacin, pefloxacin, lomefloxacin, fleroxacin, tosulfloxacin, temafloxacin, and rufloxacin. In accordance with another embodiment, the peptides or proteins of the present invention may be administered for the purposes hereinabove described in combination with one another. 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 SUBSTITUTE SHEET 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 1, 2, and 3 are prepared at a concentration of 512 μg/ml in sterile deionized distilled water and stored_at -70°C. Peptide 1 has the following structural .formula: (SEQ ID NO:27)-NHCH 2 CH 2 OH. Peptide 2 has the following structural formula: (SEQ ID NO:27)-NHCH 2 CH 2 NH 2 . Peptide 3 has the following structural formula: (SEQ ID NO:27)-NH 2 . 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/ l of either S. aureus ATCC 25923, E. coli ATCC 25922, or P. aeruginosa 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. eruginosa, and E is the MIC of the peptide against E.coli. TABLE I Peptide MIC (uq/ml) 1 4,8 2 16 3 IB SUBSTITUTESHEET The above results indicate that a biologically active peptide having a C-terminal ethanolamine group provided increased biological activity as opposed to the same peptide having an unsubstituted C-terminal amide. The peptides or proteins 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 or protein 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 or protein 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 or proteins may be administerd either alone or in combination with an ion having pharmacological properties, antibiotic, or ion channel forming peptide or protein as hereinabove described. When the peptide or protein is administered in combination with an ion having pharmacological properties, the activity of the peptide or protein is potentiated. When the peptide or protein is administered in combination with an agent as' hereinabove described, it is possible to SUBSTITUTE SHEET administer the peptide or protein and agent in separate forms. For example, the agent may be administered systemically and the peptide or protein may be administered topically. When the peptide or protein is adminitered 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 or protein 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 or protein 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. SUBSTITUTESHEET SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: Kari, U. Prasad Maloy, W. Lee (ii) TITLE OF INVENTION: Composition and Treatment with Biologically Active Peptides Having C-Terminal Substitutions (iii) NUMBER OF SEQUENCES: 113 (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 (Vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: 07713716 (B) FILING DATE: 12-JUN-1991 (C) CLASSIFICATION: SUBSTITUTESHEET ( ii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: (B) FILING DATE: (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Olstein, Elliot M. (B) REGISTRATION NUMBER: 24,025 . . (C) REFERENCE/DOCKET NUMBER: 421250-119 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: 201-994-1700 (B) TELEFAX: 201-994-1744 (2) INFORMATION FOR SEQ ID NO:l: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 20 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (x) PUBLICATION INFORMATION: (H) DOCUMENT NUMBER: W089/11290 (I) FILING DATE: 19-MAY-1989 (J) PUBLICATION DATE: 30-NOV-1989 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l: Ala Phe Ser Lys Ala Phe Ser Lys Ala Phe 5 10 Ser Lys Ala Phe Ser Lys Ala Phe Ser Lys 15 20 (2) INFORMATION FOR SEQ ID NO:2: SUBSTITUTESHEET (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 24 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (x) PUBLICATION INFORMATION: (H) DOCUMENT NUMBER: W089/11290 (I) FILING DATE: 19-MAY-1989 (J) PUBLICATION DATE: 30-NOV-1989 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: Ala Phe Ser Lys Ala Phe Ser Lys Ala Phe 5 10 Ser Lys Ala Phe Ser Lys Ala Phe Ser Lys 15 20 Ala Phe Ser Lys (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 16 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear ( ii ) MOLECULE TYPE : peptide (x ) PUBLICATION INFORMATION: (H) DOCUMENT NUMBER: W089/11290 ( I ) FILING DATE : 19-MAY-1989 ( J) PUBLICATION DATE : 30-NOV-1989 SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: Phe Ser Lys Ala Phe Ser Lys Ala Phe Ser 5 10 Lys Ala Phe Ser Lys Ala 15 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 20 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (x) PUBLICATION INFORMATION: (H) DOCUMENT NUMBER: W089/11290 (I) FILING DATE: 19-MAY-1989 (J) PUBLICATION DATE: 30-NOV-1989 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: Ser Lys Ala Phe Ser Lys Ala Phe Ser Lys 5 10 Ala Phe Ser Lys Ala Phe Ser Lys Ala Phe 15 20 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 16 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (x) PUBLICATION INFORMATION: (H) DOCUMENT NUMBER: W089/11290 (I) FILING DATE: 19-MAY-1989 (J) PUBLICATION DATE: 30-N0V-1989 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: Lys Ala Phe Ser Lys Ala Phe Ser Lys Ala 5 10 Phe Ser Lys Ala Phe Ser 15 (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 23 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: Magainin I peptide. (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proc. Nat. Acad. Sci. (D) VOLUME: 84 (F) PAGES: 5449-5453 (G) DATE: AUO - 1987 (H) DOCUMENT NUMBER: US 4810777 ( I ) FILING DATE : 04-MAR-1987 ( J) PUBLICATION DATE : 07-MAR-1989 SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6 Gly He Gly Lys Phe Leu His Ser Ala Gly 5 10 Lys Phe Gly Lys Ala Phe Val Gly Glu He 15 20 Met Lys Ser (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 23 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: Magainin II peptide. (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proc. Nat. Acad. Sci. (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 SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7 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:8: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 22 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: Magainin III peptide. (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proc. Nat. Acad. Sci. (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 SUBSTITUTE SHEET ( i) SEQUENCE DESCRIPTION: SEQ ID NO:8 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 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 22 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: magainin peptide. (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proc. Nat. Acad. Sci. (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 SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: 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:10: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: magainin peptide. (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proc. Nat. Acad. Sci. (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 SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: 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:11: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 20 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: magainin peptide. (x) PUBLICATION INFORMATION: (A) AUTHOR: Zasloff, Michael (C) JOURNAL: Proc. Nat. Acad. Sci. (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:11: Lys Phe Leu His Ser Ala Lys Lys Phe Gly 5 10 Lys Ala Phe Val Gly Glu He Met Asn Ser 15 20 SUBSTITUTESHEET (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: PGLa peptide. (x) PUBLICATION INFORMATION: SUBSTITUTESHEET (xi) SEQUENCE DESCRIPTION: SE ID NO:12. 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:13: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 25 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: XPF peptide. (x) SUBSTITUTESHEET ( 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:13: 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:14: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Kreil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 SUBSTITUTE SHEET (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:14: 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:15: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear SUBSTITUTESHEET (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15 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:16: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (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 SUBSTITUTE SHEET (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:16: 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:17: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (x) PUBLICATION INFORMATION: SUBSTITUTE SHEET ( i) SEQUENCE DESCRIPTION: SEQ ID NO:17: 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 SUBSTITUTESHEET (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (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 SUBSTITUTE SHEET ( 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:18: 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:19: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (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 . SUBSTITUTE SHEET 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:19: 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 Ala Pro Gin Gin 25 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide SUBSTITUTE SHEET ( ix) EEATURE : (A) NAME/KEY: CPF peptide. (X) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. SUBSTITUTESHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: 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:21: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (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 SUBSTITUTE SHEET (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: 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:22: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide . (x) PUBLICATION INFORMATION: SUBSTITUTE SHEET (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:22: 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:23: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids SUBSTITUTE SHEET (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (x) SUBSTITUTESHEET (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: 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:24: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (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 SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: 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:25: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K. Egger, R. Kreil SUBSTITUTE SHEET (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:25 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:26: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: SUBSTITUTE SHEET (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (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 SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: 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 (2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: 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:28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear ( ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: 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:29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: 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:30: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: 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:31: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: 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:32: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear ( ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: 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:33: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: 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:34: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: 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:35: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: 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:36: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear ( ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: 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:37: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:37: 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:38: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: 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:39: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: 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:40: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa i s ornithine SUBSTITUTE SHEET ( i) SEQUENCE DESCRIPTION: SEQ ID NO: 0: 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:41: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: Lys He Ala Arg He Ala Gly Lys He Ala 5 10 Arg He Ala Gly Lys He Ala Arg He Ala 15 20 Gly (2) INFORMATION FOR SEQ ID NO:42: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is orni thine SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: 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:43: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: 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:44: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION : Xaa is norleucine SUBSTITUTE SHEET -82- ( i) SEQUENCE DESCRIPTION: SEQ ID NO: 4: Lys Xaa Ala Gly Lys Xaa Ala Lys Xaa Ala 5 10 Gly Lys Xaa Ala Lys Xaa Ala Gly Lys Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO:45: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is norleucine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: Lys Xaa Ala Gly Lys He Ala Lys Xaa Ala 5 10 Gly Lys He Ala Lys Xaa 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 (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE : peptide SUBSTITUTE SHEET ( ix ) FEATURE : (D) OTHER INFORMATION: Xaa is norleucine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: Lys He Ala Gly Lys Xaa Ala Lys He Ala 5 10 Gly Lys Xaa Ala Lys He Ala Gly Lys Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO:47: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is norvaiine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: Lys Xaa Ala Gly Lys Xaa Ala Lys Xaa Ala 5 10 Gly Lys Xaa Ala Lys Xaa Ala Gly Lys Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO:48: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear SUBSTITUTESHEET (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is norvaiine (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: Lys Xaa Ala Gly Lys He Ala Lys Xaa Ala 5 10 Gly Lys He Ala Lys Xaa Ala Gly Lys Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO:49: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: Lys Leu Leu Ser Lys Leu Gly Lys Leu Leu 5 10 Ser Lys Leu Gly Lys Leu Leu Ser Lys Leu 15 20 Gly (2) INFORMATION FOR SEQ ID NO:50: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear SUBSTITUTE SHEET (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:50: 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:51: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear ( ii ) MOLECULE TYPE : peptide ( ix) FEATURE: (D) OTHER INFORMATION: Xaa is norvaiine ( i) SEQUENCE DESCRIPTION: SEQ ID NO:51: Lys He Ala Gly Lys Xaa Ala Lys He Ala 5 10 Gly Lys Xaa Ala Lys He Ala Gly Lys Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO:52: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear SUBSTITUTE SHEET (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52: 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:53: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53: • Ala Gly Lys He Ala Lys He Ala Gly Lys 5 10 He Ala Lys He Ala Gly Lys He Ala Lys 15 20 He (2) INFORMATION FOR SEQ ID NO:54: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: 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:55: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:55: 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:56: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide SUBSTITUTE SHEET (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:56 Arg He Ala Gly Arg He Ala Arg He Ala 5 10 Gly Arςr He Ala Arg He Ala Gly Arg He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:57: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:57: 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:58: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids " (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:58: 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:59: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:59: 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:60: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is orni thine SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:60: Xaa He Ala Gly Xaa He Ala Xaa He Ala 5 10 Gly Xaa He Ala Xaa He Ala Gly Xaa He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:61: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:61: 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:62: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide SUBSTITUTE SHEET (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:62: 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:63: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is cyclohexylalanine (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:63: Lys Xaa Ala Gly Lys He Ala Lys Xaa Ala 5 10 Gly Lys He Ala Lys Xaa 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 (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide SUBSTITUTE SHEET (ix) FEATURE : (D) OTHER INFORMATION: Xaa is norleucine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:64: Lys Xaa Ala Lys He Ala Gly Lys Xaa Ala 5 10 Lys He Ala Gly Lys Xaa Ala Lys He Ala 15 20 Gly (2) INFORMATION FOR SEQ ID NO:65: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acids (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:65: 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:66: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET ( ix) FEATURE : (D) OTHER INFORMATION: Xaa is homoarginine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:66: Xaa He Ala Gly Xaa He Ala Xaa He Ala 5 10 Gly Xaa He Ala Xaa He Ala Gly Xaa He 15 20 Ala (2)INFORMATION FOR SEQ ID NO:67: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: Xaa is p-aminophenylalanine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:67: 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:68: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear SUBSTITUTESHEET (ii) MOLECULRE TYPE: peptide (ix) FEATURE: Xaa is p-aminophenylalanine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:68: 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:69: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 24 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:69: 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 Lys He Ala (2) INFORMATION FOR SEQ ID NO:70: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:70: Lys Leu Ala Ser Lys Ala Gly Lys lie Ala Gly 5 10 Lys He Ala Lys Val Ala Leu Lys Ala Leu 15 20 (2) INFORMATION FOR SEQ ID NO:71: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is ornithine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71: Lys He Ala Gly Lys He Ala Lys He Ala Gly 5 10 Xaa He Ala Lys He Ala Gly Lys He Ala 15 20 (2) INFORMATION FOR SEQ ID NO:72: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear ( ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:72: 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:73: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) FEATURE: (D) OTHER INFORMATION: Xaa is norleucine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:73: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Xaa He Ala Lys He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:74: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is norvaiine SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Xaa He Ala Lys He Ala Gly Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:75: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is ornithine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:75: Lys Phe Ala Gly Lys Phe Ala Lys Phe Ala Gly 5 10 Xaa Phe Ala Lys Phe Ala Gly Lys Phe Ala 15 20 (2) INFORMATION FOR SEQ ID NO:76: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear ( ii ) MOLECULE TYPE : peptide ( ix) FEATURE : SUBSTITUTE SHEET (D) OTHER INFORMATION: Xaa is orni hine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76: Lys He Ala Gly Lys Phe Ala Lys He Ala 5 10 Gly Xaa Phe Ala Lys He Ala Gly Lys Phe 15 20 Ala (2) INFORMATION FOR SEQ ID NO:77: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa at residues 6, 13, and 20 is norleucine, Xaa at residue 12 is ornithine ( i) SEQUENCE DESCRIPTION: SEQ ID NO:77: Lys He Ala Gly Lys Xaa Ala Lys He Ala 5 10 Gly Xaa Xaa Ala Lys He Ala Gly Lys Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO:78: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid SUBSTITUTE SHEET (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:78: 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:79: (i.) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:79: 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:80: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear SUBSTITUTE SHEET (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is norleucine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:80: Lys He Ala Ser Lys Ala Gly Lys Xaa Ala 5 10 Gly Lys He Ala Lys Val Ala Leu Lys Ala Leu 15 20 (2) INFORMATION FOR SEQ ID NO:81: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii ) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is norleucine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:81: Lys Leu Ala Ser Lys Ala Gly Lys Xaa Ala 5 10 Gly Lys He Ala Lys Val Ala Leu Lys Ala 15 20 Leu (2 ) INFORMATION FOR SEQ ID NO: 82 : (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids SUBSTITUTE SHEET (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is norleucine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:82: Lys Xaa Ala Ser Lys Ala Gly Lys Xaa Ala 5 10 Gly Lys lie Ala Lys Val Ala Leu Lys Ala Leu 15 20 (2) INFORMATION FOR SEQ ID NO:83: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is p-aminophenylalanine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:83: Lys He Ala Gly Lys He Ala Lys He Ala 5 10 Gly Xaa He Ala Lys He Ala Gly Lys He 15 20 Ala SUBSTITUTE SHEET (2) INFORMATION FOR SEQ ID NO:84: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:84: 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:85: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:85: 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:86: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids SUBSTITUTESHEET (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:86: 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:87: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:87: Lys Leu Ala Ser Lys Ala Ala Lys He Ala 5 10 Ala Lys He Ala Lys Val Ala Leu Lys Ala 15 20 Leu (2) INFORMATION FOR SEQ ID NO:88: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear ( ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:88: 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:89: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:89: Lys Phe Ala Lys Lys Phe Ala Lys Phe Ala 5 10 Lys Lys Phe Ala Lys Phe Ala Lys Lys Phe 15 20 Ala (2) INFORMATION FOR SEQ ID NO:90: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:90: Lys Phe Ala Lys Lys He Ala Lys Phe Ala 5 10 Lys Lys He Ala Lys Phe Ala Lys Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:91: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:91: 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:92: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear ( ii ) MOLECULE TYPE : peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:92: 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:93: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:93: 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:94: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide SUBSTITUTE SHEET (xi) SEQUENCE DESCRIPTION: SEQ ID NO:94: 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:95: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:95: Leu Lys Lys Leu Lys Lys Leu Leu Lys Leu 5 10 Leu (2) INFORMATION FOR SEQ ID NO:96: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:96: Leu Leu Lys Lys Leu Lys Lys Leu Leu Lys 5 10 Leu Leu SUBSTITUTESHEET (2) INFORMATION FOR SEQ ID NO:97: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 13 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:97: Lys Leu Leu Lys Lys Leu Lys Lys Leu Leu 5 10 Lys Leu Leu (2) INFORMATION FOR SEQ ID NO:98: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 14 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:98: Lys Lys Leu Leu Lys Lys Leu Lys Lys Leu 5 10 Leu Lys Leu Leu (2) INFORMATION FOR SEQ ID NO:99: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 16 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear SUBSTITUTESHEET (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:99: Lys Lys Leu Leu Lys Lys Leu Lys Lys Leu Leu Lys Lys Leu Arg Arg 5 10 15 (2) INFORMATION FOR SEQ ID NO:100: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 16 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:100: Lys Leu Lys Lys Leu Leu Lys Lys Leu Lys 5 10 Lys Leu Leu Lys Leu Leu 15 (2) INFORMATION FOR SEQ ID NO:101: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:101: Leu Lys Lys Leu Leu Lys Lys Leu Lys Lys 5 10 Leu Leu Lys Lys -Asn 15 SUBSTITUTE SHEET (2) INFORMATION FOR SEQ ID NO:102: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: xaa is ho oserine. (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:102: Leu Lys Lys Leu Leu Lys Lys Leu Lys Lys 5 10 Leu Leu Lys Lys Xaa 15 (2) INFORMATION FOR SEQ ID NO:103: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 18 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:103: Leu Lys Leu Leu Lys Lys Leu Leu Lys Lys 5 10 Asn Lys Lys Leu Leu Lys Lys Leu 15 (2) INFORMATION FOR SEQ ID NO:104: (i) SEQUENCE CHARACTERISTICS SUBSTITUTE SHEET (A) LENGTH: 18 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:104: Leu Lys Leu Leu Lys Lys Leu Leu Lys Lys 5 10 Pro Lys Lys Leu Leu Lys Lys Leu 15 (2) INFORMATION FOR SEQ ID NO:105: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 22 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:105: Leu Leu Lys Lys Leu Lys Lys Leu Leu Lys 5 10 Lys Leu Gin Gly Pro Pro Gin Gly Gin Ser 15 20 Pro Gin (2) INFORMATION FOR SEQ ID NO:106: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 20 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: SUBSTITUTE SHEET (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:106: Leu Ala Ser Lys Ala Gly Ala He Ala Gly 5 10 Lys He Ala Lys Lys Leu Leu Lys Lys Leu 15 20 (2) INFORMATION FOR SEQ ID NO:107: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:107: Leu Lys Lys Leu Lys Lys Leu 5 (2) INFORMATION FOR SEQ ID NO:108: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:108: Leu Leu Lys Lys ' Leu Lys Lys Leu 5 SUBSTITUTE SHEET (2) INFORMATION FOR SEQ ID NO:109: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:109: Lys Leu Leu Lys Lys Leu Lys Lys Leu 5 (2) INFORMATION FOR SEQ ID NO:110: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:110: Lys Lys Leu Leu Lys Lys Leu Lys Lys Leu 5 10 (2) INFORMATION FOR SEQ ID NO:111: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear SUBSTITUTE SHEET (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:111: Leu Lys Lys Leu Leu Lys Lys Leu Lys Lys Leu 5 10 (2) INFORMATION FOR SEQ ID NO:112: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 11 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:112: Ala Lys Lys Leu Leu Lys Lys Leu Lys Lys Leu 5 10 (2) INFORMATION FOR SEQ ID NO:113: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 14 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:113: Leu Lys Lys Leu Leu Lys Lys Leu Lys Lys Leu 5 10 Leu Lys Arg SUBSTITUTESHEET

Claims: WHAT IS CLAIMED IS: 1. A C-terminal substituted peptide or protein of the formula: 0 X - C II - T, wherein X is a biologically active amphiphilic peptide or protein, said peptide or protein being an ion channel-forming peptide or protein, and T is selected from the group consisting of: (a) 0-R, wherein R is a substituted or unsubstituted aliphatic, aromatic, or aralkyl group having from 1 to 10 carbon atoms; (b) NH-NH 2 ; (c) NH-OH; and (d) \V N ' R", wherein R ! and R" are hydrogen or selected from the class consisting of group (i) and group (ii), wherein group (i) is a hydroxy-substituted aliphatic, aromatic or aralkyl group having no more than 10 carbon atoms, and group (ii) is an amino-substituted aliphatic, aromatic, aralkyl, or alkylaromatic group, and at least one of R 1 and R" is group (i) or group (ii) . 2. The peptide of Claim 1 wherein T is NH-CH 2 CH 2 ~OH. 3. The peptide of Claim 1 wherein T is NH-CH 2 CH 2 -NH 2 . 4. The peptide of Claim 1 wherein X is a magainin peptide. 5. The peptide of Claim 1 wherein X is a PGLa peptide. 6. The peptide of Claim 1 wherein X is an XPF peptide. 7. The peptide of Claim 1 wherein X is a CPF peptide. 8. The peptide of Claim 1 wherein X is a cecropin. 9. The peptide of Claim 1 wherein X is a sarcotoxin. 10. The peptide of Claim 1 wherein X includes one of the following basic structures X-,. through X 3 -,, wherein: X 31 is "tR 3l "R 32 "R 32 "R 33 "R 3l "R 32 "R 32 ] n "; SUBSTITUTE SHEET X 32 is "tR 32 "R 32 " 33 "*R 3l "R 32 "R 32 "R 31 ] n " X 33 iS "tR 32~ R 33 "R 3l "R 32 "R 32 "R 3l "R 32 ] n " X 34 is -[ R 33- 31 - 32 "R 32 'R 3l "R 32 "R 32 ] n " X 35 is "[R 3 R 32 "R 32 "R 3l "R 32 "R 32 "R 33 ] n " X 36 is "[R 32 "R 32~ R 3l "R 32 "R 32~ R 33 "R 31 * n~ and X 37 iS "[R 32 "R 3l " 32 "R 32 "R 33 "R 3l "R 32 ] n " ' wherein R 31 is a basic hydrophilic amino acid, R 32 is a hydrophobic amino acid, R 33 is a neutral hydrophilic, or hydrophobic amino acid, and n is from 2 to 5. 11. The peptide of Claim 1 wherein X includes the following basic structure XJ Q : R 31~ R 32~ R 32~ R 33~ R 34~ R 32~ R 32~ R 31~ R 32~ R 32~ R 32~ R 34~ R 32~ R 32' wherein R... is a basic hydrophilic amino acid, R 32 is a hydrophobic amino acid, R__ is a neutral hydrophilic or hydrophobic amino acid, and R 34 is a basic hydrophilic or hydrophobic amino acid. 12. The peptide of Claim 11 wherein X includes the following structure: Y4.0-.-X4.0 r wherein X4.0-. is as hereinabove described in Claim 11, and Y 4Q is: (i) R 32 -, or (ϋ) R 32 "R 32 "; or (iii) R 34 "R 32 "R 32 ; θr (iv) R 33 "R 34 "R 32 "R 32 ; or (v) R 32~ R 33 "R 34~ R 32~ R 32 ; Qr (vi) R 32 "R 32~ R 33~ R 34 "R 32~ R 32 ; ° r (vii) R 3l "R 32 "R 32 'R 33 "R 34 "R 32 _R 32 * 13. The peptide of Claim 11 wherein X includes the following structure: X.-.-Z wherein X 40 is as hereinabove described in Claim "40 40' 11, and Z 40 is: (i) R 31 -, or (ii) R 31- R 32 "; or (iii) R 3l "R 32 "R 32 ; or SUBSTITUTESHEET ( iv ) R 31- R 32- R 32- R 33 ; or ( v ) R 3l "R 32 "R 32 "R 33 "R 34 ; or ( vi ) R 3l "R 32 "R 32 "R 33 'R 34 "R 32 ; ° r (vii ) R 3l "R 32~ R 32~ R 33 -R 34 "R 32~ R 32 * 14. The peptide of Claim 11 wherein X includes the following structure: (Y 40 ) a" X 40" (Z 40 ) b / wherein Y 4Q and Z 4Q are as previously defined in Claims 12 and 13, a is 0 or 1, and b is 0 or 1. 15. The peptide of Claim 1 wherein X includes the following structure ςn : - R 4 R 42- R 42- R 4l "R 42- R 42- R 41- R 41- R 42- R 4r R 41' wherein R 41 is a hydrophobic amino acid, and R 4 _ is a basic hydrophilic or neutral hydrophilic amino acid. 16. The peptide of Claim 1 wherein X includes the following structure X-.-,: "R 42 "R 41 _R 42 "R 42 "R 4l "R 4 R 42- R 42- R 41- R 42 _R 42' wherein R 41 is a hydrophobic amino acid, and R 42 is a basic hydrophilic or neutral hydrophilic amino acid. 17. The peptide of Claim 1 wherein X includes the following structure X-.: _R 4l "R 42 "R 42 "R 4l "R 4l "R 42 "R 42 "R 4l "R 42 "R 42 "R 4l 'R 4l "R 42 "R 42 "R 43' wherein R.. is a hydrophobic amino acid, R 42 is a basic hydrophilic amino acid or neutral hydrophilic amino acid, and R 43 is a neutral hydrophilic amino acid. 18. The peptide of Claim 1 wherein X includes the following structure X ςg " ~ R 4l" R 42~ R 4l" R 41~ R 42 "R 42 "R 4l "R 41~ R 42" R 42 "R 44' wherein R 41 is a hydrophobic amino acid, R 42 is a basic hydrophilic or neutral hydrophilic amino acid, and R 44 is a neutral hydrophilic amino acid or proline. 19. The peptide of Claim 1 wherein X includes the following structure X 5 g- SUBSTITUTE SHEET "R 4l "R 41~ R 42 "R 42 "R 4l "R 42 "R 42 "R 4l 'R 4l "R 42 "R 42 "R 42 "R 4l "R 43' wherein R 4 - is a hydrophobic amino acid, R 42 is a basic hydrophilic or neutral hydrophilic amino acid, and R 43 is a neutral hydrophilic amino acid. 20. The peptide of Claim 1 wherein X includes the following structure X6 c 0 n : _R 4l "R 4l "R 43 "R 42 "R 4l "R 4l "R 4l "R 4l "R 4l "R 4l "R 42 "R 4l "R 4l "R 42 "R 42 " R 41 ~ R 41 ~ R 42 ~ R 42 -R 41 ' wherein R 4 - is a hydrophobic amino acid, R._ is a basic hydrophilic or netural hydrophilic amino acid, and R._ is a neutral hydrophilic amino acid. 21. The peptide of Claim 1 wherein X has a structure selected from the group consisting of: ( a ) R 41 -R 4 2- R 4 2 "R 4l "R 42 'R 42 "R 41 ; ( b ) R 41 - R 41 - 42- R 4 2 "R 41 "R 42 "R 42 "R 41 ; ( c ) 2 - R 4i- R 4i- R 42 "R 42 "R 4l "R 42 "R 42 "R 41 ; ( - ~ ) R 4 2 ~ R 4 2 "R 4i~ R 4i~ R 4 "R 4 2 "R 4i~ R 42 _R 42~ R 41 ; and (e) R 41 - R 42 - 42 - R 41 - R 41 - R 42 - R 42- R R 42- R 42- R 41' wherein R 41 is a hydrophobic amino acid and R 42 is a basic hydrophilic or neutral hydrophilic amino acid. 22. A process for inhibiting the growth of a target cell, virus, or virally-infected cell in a host, comprising: administering to a host a C-terminal substituted peptide or protein of the formula: O X- iCf-T, wherein X is a biologically active amphiphilic peptide or protein, said peptide or protein being an ion channel-forming peptide or protein, and T is selected from the group consisting of: (a) 0-R, wherein R is a substituted or unsubstituted aliphatic, aromatic, or aralkyl group having from 1 to 10 carbon atoms; (b) NH-NH 2 ; (c) NH-OH; and SUBSTITUTESHEET ( d ) R ' N R", wherein R' and R" are hydrogen or selected from the class consisting of group (i) and group (ii), wherein group (i) is a hydroxy-substituted aliphatic, aromatic or aralkyl group having no more than 10 carbon atoms, and group (ii) is an amino-substituted aliphatic, aromatic, aralkyl, or alkylaromatic group, and at least one of R 1 and R" is group (i) or group (ii) . wherein R 1 and R" are hydrogen or selected from the class consisting of group (i) and group (ii), wherein group (i) is (CH 2 ) n ~OH; and group (ii) is (CH 2 ) n - H 2 , wherein n is from 1 to 10, and wherein at least one of R' and R" is group (i) or group (ii). 23. The process of Claim 22 wherein T is NH-CH 2 CH 2 -OH. 24. The process of Claim 22 wherein T is NH-CH 2 CH 2 -NH_. 25. The process of Claim 22 wherein X is a magainin peptide 26. The process of Claim 22 wherein X is a PGLa peptide. 27. The process of Claim 22 wherein X is an XPF peptide. 28. The process of Claim 22 wherein X is a CPF peptide. 29. The process of Claim 22 wherein X is a cecropin. 30. The process of Claim 22 wherein X is a sarcotoxin. 31. The process of Claim 22 wherein X includes one of the following basic structures X 3 - through X 37 / wherein: X '3.1 is -l 3 1 - R 3 2 - R 3 2 - R 33- R 3 1 - R 32 - R 3 2 n C 32 is ~- R 32~ R 32 -R 33 _R 3l "R 32 "R 32~ R 31 n " X33 is ~- R 32~ R 33 -R 31~ R 32 "R 32~ R 31~ R 32 n " X34 is ~ [R 33 -R 31~ R 32~ R 32~ R 3l ""R 32~ R 32 n " X35 is -[R 31 -R 32 -R 32 -R 31 -R 32 -R 32 -R 33 n X36 is " - R 32 "R 32 "R 3l "R 32 _R 32 "R 33 _R 31 n .-' and [ 37 is " - R 32 "R 3l "R 32 "R 32~ R 33~ R 3l "R 32 n' wherein R 31 is a basic hydrophilic amino acid, R 32 is a hydrophobic amino acid, SUBSTITUTE SHEET R__ is a neutral hydrophilic or hydrophobic amino acid, and n is from 2 to 5. 32. The process of Claim 22 wherein the X includes the following basic structure 4Q : R 3l "R 32 "R 32 "R 33 -R 34 "R 32 "R 32 "R 3l "R 32 "R 32 "R 32 "R 34 "R 32 "R 32' wherein R 3 _ is a basic hydrophilic amino acid, R 32 is a hydrophobic amino acid, R,- is a neutral hydrophilic or hydrophobic amino acid, and R„. is a basic hydrophilic or hydrophobic amino acid. 33. The process of Claim 32 wherein X includes the following structure: Y4 / i0 n - 4 / j0- wherein X4 Λ 0 r . is as herienabove described in Claim X4j.0-.-Z4 Λ 0 ι , wherein X4-0-, is as hereinabove described in Claim 32, and Z 4Q is: (i) R 31 -; or (ii ) R 31- R 32~ ? or (iii ) R 31- R 32~ R 32 ; ° r ( iv) R 31 -R 32 -R 32 -R 33 ; or < V > R 31- R 32- R 32- R 33 "R 34 ; or (vi ) R 31~ R 32" R 32 "R 33 "R 34 "R 32 ; ° r ( vii ) R 3l" R 32~ R 32 "R 33 "R 34 "R 32 "R 32- 35. The process of Claim 32 wherein the peptide includes the following structure: (Y 40 ) a" X 40" (Z 40 ) b' wherein Y 4Q and Z 4(J are as previously defined in Claims 33 and 34, a is 0 or 1, and b is 0 or 1. SUBSTITUTESHEET 36. The process of Claim 22 wherein X includes the following structure X 50 " - R 4l "R 42 "R 42 "R 4l "R 42 "R 42 "R 4l "R 4l "R 42 "R 4l "R 41' wherein R 41 is a hydrophobic amino acid, and R 42 is a basic hydrophilic or neutral hydrophilic amino acid. 37. The process of Claim 22 wherein X includes the following structure X 52 : ■R 42" R 4l" R 42~ R 42~ R 4l" R 41~ R 42~ R 42" R 41~ R 42" R 42' wherein R 41 is a hydrophobic amino acid, and R._, is a basic hydrophilic or neutral hydrophilic amino acid. 38. The process of Claim 22 wherein X includes the following structure X 54 * -R 4l "R 42 "R 42 "R 4l "R 4l "R 42 "R 42~ R 41~ R 42 "R 42 "R 41~ R 4l "R 42~ R 42 "R 43' wherein R 41 is a hydrophobic amino acid, R 42 is a basic hydrophilic or neutral hydrophilic amino acid, and R.« is a neutral hydrophilic amino acid. 39. The process of Claim 22 wherein X includes the following structure 5β " ~ R 4l "R 42 "R 4l "R 4l "R 42~ R 42~ R 41~ R 4l "R 42~ R 42 "R 44' wherein R 41 is a hydrophobic amino acid, R 42 is a basic hydrophilic or neutral hydrophilic amino acid, and .. is a neutral hydrophilic amino acid or proline. 40. The process of Claim 22 wherein X includes the following structure X-_: "R 4l" R 4l "R 42 "R 42" R 4l "R 42 "R 42 "R 4l "R 4l "R 42 'R 42 "R 42 "R 4l "R 43' wherein R 41 is a hydrophobic amino acid, R 42 is a basic hydrophilic or neutral hydrophilic amino acid, and R 43 is a neutral hydrophilic amino acid. 41. The process of Claim 22 wherein X includes the following structure X g « "R 4l "R 4l "R 43 "R 42~ R 4l "R 4l "R 4l "R 4l "R 4l "R 4l "R 42 "R 4l "R 41~ R 42 "R 42 "R 4l " -R 41 -R 42 -R 42 -R 41 -, wherein R 41 is a hydrophobic amino acid, R 42 is a basic hydrophilic or neutral hydrophilic amino acid, and R 43 is a neutral hydrophilic amino acid. SUBSTITUTE SHEET 42. The process of Claim 22 wherein X has a structure selected from the group consisting of: (a) R 41 - R 42 - R 42 "R 41 "R 42 'R 42 "R 41 ; (b) R 4 2 - R 41 - 42 - R 2 - R 4i- R 4 2 - R 42- R 41 ; (c) R 2 - R 4i- R 4l "R 42 "R 42 "R 4l "R 42 "R 42 "R 41 ; ( d ) 42 - R 4 2 - R 4l "R 4l "R 42 "R 42 "R 4l "R 42 "R 42 "R 41 ; and ( e ) R 41 -R42-R 2 "R 4l " ^.l "R 42- R 42 "R 41- R 42- R 42 "R 41' wherein R._ is a hydrophobic amino acid, and R 42 is a basic hydrophilic or neutral hydrophilic amino acid. 43. The process of Claim 22 wherein the peptide is administered in an amount effective in inhibiting growth of a target cell, virus or virally-infected cell. SUBSTITUTESHEET

Inventors: KARI U PRASAD, MALOY W LEE, KARI, U., PRASAD, MALOY, W., LEE
Applicants: MAGAININ PHARMA, MAGAININ PHARMACEUTICALS, INC.
Application year: 1992
Main classification: C07K7
IPC codes: A61K38, A61P31, C07K7, C07K14