TREATMENT OF DERMATOLOGICAL MALIGNANCIES WITH BIOLOGICALLY ACTIVE PEPTIDES

Abstract: A process for treating a dermatological malignancy, such as melannoma, in a host which comprises administering to the host at least one biologically active amphiphilic peptide or protein. The peptide or protein may be administered intralesionally, whereby the peptide or protein may inhibit, prevent, or destroy the growth of the dermatological malignancy.

Description: TREATMENT OF DERMATOLOGICAL MALIGNANCIES WITΗ BIOLOGICALLY ACTIVE PEPTIDES This invention relates to the treatment of r.ermatological malignancies, such as melanoma. More particularly, this invention relates to the treatment of •iermatological malignancies by administering a biologically active peptide or protein. In accordance with an aspect of the present invention, there is provided a process for treating a derπatological malignancy in a host comprising administering to a host at least one biologically active amphiphilic peptide or protein. The peptide or protein is an ion channel-forming peptide or protein. The peptide or protein is administered in an amount effective to treat a dermatological malignancy in a host. The term "treating a dertnatological malignancy" as used herein means that the peptide or protein prevents, inhibits, or destroys the growth of a dermatological malignancy or skin cancer, and/or reduces the size of or eliminates the dermatological malignancy. 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. 5072-5076 (July 1988) * describes methodology which indicates whether or not a peptide has ion channel-forming properties and is therefore an ionophore. As used herein an ion channel-forming peptide or ion channel-forming protein is a peptide or protein which has ion channe1-forming properties as determined by the method of Christensen, et al. An amphiphilic peptide or protein is a peptide or protein which includes both hydrophobic and hydrophilic peptide or protein regions. 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-helix. When the peptide is placed in water, it does not assume an amphiphilic structure. When the peptide encounters an oily surface or membrane, the peptide chain folds upon itself into a rodlike structure. In general, such peptides have at least 7 amino acids, and in many cases have at least 20 amino acids. In most cases, such peptides do not have in excess of 40 amino acids. As stated hereinabove, the peptides or proteins are administered in an amount effective to treat a dermatological malignancy in a host. The peptides or proteins may be administered to a host in vivo, such as, -2- for example, through systemic administration. In one embodiment, the peptides or proteins may be administered intralesionally; i.e., the peptide or protein is injected directly into the dermatological malignancy. The peptide or protein may be administered in an amount of from about 50 μg per injection to about 100 mg per injection, preferably such that peptide dosages are from about 1 mg/kg to about 5 mg/kg body weight. The peptides or proteins may also be administered intravenously or intraperitoneally. The peptide or protein may be administered in multiple doses. In one embodiment, the peptide or protein may be administered two times a week for a period of U weeks. In another embodiment, the peptide or protein may be administered topically in an amount of from about 1 mg/kg to about 5 mg/kg of body weight. The peptides or proteins are administered in combination with an acceptable pharmaceutical carrier or vehicle such as a filler, non-toxic buffer, or physiological saline solution. The peptides or proteins may also be used in combination with adjuvants, proteas p inhibitors, or compatible drugs. Dermatological malignancies which may be treated include, but are not limited to, melanoma, basal cell carcinoma, and squamous cell carcinoma. The dermatological malignancy may be metastatic or non-metastatic. In one embodiment, the peptide is a basic (positively charged) polypeptide having at least sixteen 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, 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. 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 of C or D is a basic hydrophilic amino acid, and the other of C or D is a basic or neutral hydrophilic amino acid and may be the same or different. In one embodiment, the polypeptide chain may comprise 5 or 6 groups of this sequence. In each group, each 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 groups 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 provided 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 the biologically active polypeptide may comprise 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 having 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. The resulting polypeptide chain, therefore, may have one of the following sequences: (X-) (A-B-C-D Y.), l a n i (X 2 ) a (B-C-D-A) n (Y 2 ) b (X 3 ) β (C-D-A-B) n (Y 3 ) b (X 4 ) fl (D-A-B-C) n (Y 4 ) b wherein X is D; C-D- or B-C-D-, Y j is -A or -A-B or -A-B-C X 2 is A-, D-A- or C-D-A- Y is -B, -B-C or B-C-D X 3 is B-, A-B-, D-A-B- Y 3 is -C, -C-D, -C-D-A X^is C-, B-C-, A-B-C-- Y A 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 such peptides, there may be mentioned. I Ala-Phe-Ser-Lys-Ala-Phe-Ser- ys-Ala-Phe-Ser- Lys-Ala-Phe-Ser-Lys-Ala-Phe-Ser-Lys (SEQ I 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-T.ys. (SEQ ID NO:2) III Ph ~ " -Lys-Ala-Phe-Ser- Lys-Ala-Phe-Ser-Lys-Ala- Phe-Ser-Lys-Ala- (SEQ ID NO: 3) IV Ser-Lys-Ala-Phe-Ser-Lys-Ala- Phe-Ser-Lys-Ala-Phe-Ser-Lys-Ala- Phe-Ser-Lys-Ala-Phe- (SEQ ID NO:4) 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. In accordance with another 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 peptides preferably include the following basic peptide structure X 17 : " R ir R i R 12~ R 13 "R ir R 14 "R 12 "R π " R 14 "R 12 'R i R ir R n "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 j » fl 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 where R. . , R. - , R- , and , ^ are as previously defined. A magainin peptide may also have the following structure: "X 12 "Z 12 " wherein X is as previously defined and Z' is: (i) R-, where R , is a basic hydrophilic amino acid or asparagine or glutamine. (ii) R.--R 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: where ,-, Y,~ and Z-„ are as previously 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 ir R 14a 'R 12 "R ir R U "R 12 "R 13 " R i R 14 "R 12 "R ll 'R n "R 12 ' ' whereln R H' R 12' R 13' R 14' βnd R,, are amino acids as hereinabove described. 14a The magainin peptide may also include the following structure X-.-Z..; wherein X., is the hereinabove described basic peptide structure and Z „ is R ll V (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 ll' R 14' R 14a' R 15' R 16' ^ R 17 are as hereinabove 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) (OH) or (NH 2 (Magainin I) (b) (SEQ ID NO:7) (OH) or (NH 2 ) (Magainin II) (c) (SEQ ID N0:8) (OH) or (NH 2 ) (Magainin III) The following are examples of peptide derivatives or analogs of the basic structure: (d) (SEQ ID N0:9) (OH) or (NH 2 ) (e) (SEQ ID NO: 10) (OH) or (NH 2 ) (f) (SEQ ID NO: 11) (OH) or (NH 2 ) 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 X-, : - R n - R 17 - R 12 - R ι R κ "R i "R ιr R ιr R i "R i2 "R π "R ιr R i2 "R ι R ι R π "R i2 " where R , R , R , and R _ are as previously 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 is 14 (i) R π ; (ii) R -R n where R.. and R., 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-, is: (i) R n ; or (ii) R n -R n where R is as previously defined. A PGLa peptide may also have the following structure: (Y ) ~ X 1 ~^ Z 1 ^ I 14 a x A b where X.,; Y., and Z., 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 .: "R H "R 17 "R 12 'R i R 14 "R 18 "R 17 " R ι R i4 "R i2 "R π "R ιr R i2 " R n -R n - * 1 --* l2 * 1 -) n -* n -- ~ wherein R ll' R 12' R 14' R 15 βnd R 17 βre &S P reviousl y defined and R is glutamine or asparagine or a basic lo 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,, is as previously defined and Y,., is lo 16 (i) R π or (ϋ) R 14 -R n where R . and R , are as previously defined. An XPF peptide may include the following structure: "X 16 "Z 16 " where X , is as previously defined and Z., is (i) R χl ; or (iii) R -R -Proline; or (iv) R 11 -R lg -Proline-R 12 An XPF peptide may also have the following structure: where X.-, Y., and Z., 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) (NH 2 ) 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 derivative 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 X- n : "R 2l 'R 2l "R 22 "R 22 "R 2l "R 2l "R 23 'R 2 "R 2l "R 2l "R 23 "R 2l "R 2Γ R 24 "R 25 "R 2 Γ wherein R_ is a hydrophobic amino acid; R„„ is a hydrophobic amino acid or a basic hydrophilic amino acid; R_, is a basic hydrophilic amino acid; R„, is a hydrophobic or neutral hydrophilic amino acid; and R__ is a basic or neutral hydrophilic amino acid. The hereinabove basic structure is hereinafter symbolically indicated as X ?f .. The hydrophobic amino acids are Ala, Cys, Phe, Gly, lie, Leu, Met, Val, Trp, Tyr, norleucine (Nle), norvaline (Nva), and cyclohexylalanine (Cha). The neutral hydrophilic amino acids are Asn, Gin, Ser, Thr, and homoserine (Hse). The basic hydrophilic amino acids are Lys, Arg, His, Orn, homoarginine (Har), 2,4-diarainobutyric 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) R 22 _R 25 '; or (iii) R 2l "R 22~ R 25 ; ° r (iv) R 22 "R 2l 'R 22 "R 25 ; P referabl y Glycine - R 21 "R 2 2~ R 25" wherein R_-, R 2 „ and R_,- are as previously 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 2Q is (i) R 21 -, or (ii) R 2l "R 2l "; ° r (iii) R 2l "R 2l "R 24 ; ° r ( v ) R 2 r R 2 r R 24- R 24- R 26 ; 0r ( v i R 2 r R 2 r R 2 4- R 2 4- R 26 _Gln ; or (vii) R 21 -R 21 -R 24 -R 24 -R 26 -Gln-Gln, wherein R 2J and R , are as previously defined, and R , is proline or a hydrophobic amino acid. Preferred peptides may be represented by the following structural formula wherein X 2n> Y ?n and Z_. are as previously defined 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 N0:22) (SEQ ID N0:23) (SEQ ID NO:24) (SEQ ID NO:25) (SEQ ID NO:26) A review of the CPF peptides can be found in Richter, . , 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_- through X__ wherein: X 31 is "[R 3 R 32 "R 32 'R 33 "R 3l 'R 32 "R 32 ]" n X 32 1S " [ R 32 'R 32 "R 33 'R 3r R 32~ R 32 "R 31 3 " n X 33 is " [ R 32 "R 33 "R 3r R 32 _R 32 'R 3r R 32 ] ' n X 34 is " [ R 33 "R 3 R 32 "R 32 'R 3 R 32 "R 32 ] " n X 35 iS " I R 3l "R 32 "R 32 "R 3 R 32 "R 32 "R 33 ] " n and X 36 ls " f R 32 "R 32 'R 3 R 32 "R 32 'R 33 "R 31 ] " n X 37 is " I R 32 "R 3l "R 32 "R 32 "R 33 'R 3r R 32 ] " n wherein R 3 - is a basic hydrophilic amino acid, R - is a hydrophobic amino acid, R_, is a neutral hydrophilic, basic 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, Pro, Val, Trp and Tyr.norleucine (Nle), norvaline (Nva), and cyclohexylalanine (Cha). The neutral hydrophilic amino acids may be selected from the class consisting of Asn, Gin, Ser, Thr, and hσmoserine (Hse). In accordance with one embodiment, when the peptide includes the structure X-., the peptide may include the following structure: Y- ^ -X-., wherein X is as hereinabove described, and Y is: (i) R 32 ; (ii) R 32 -R 32 ; (iii) 31 - 32 - 32 ; ( v) R 32- R 33- R 3 R 32- R 32 ; ° r (vi) R 32- R 32- R 33- R 3 R 32 _R 32' wherein R 31' R 32' and R are as hereinabo e described In accordance with another embodiment, when the peptide includes the structure Xo, . the peptide may include the following structure: X,--Z,., wherein X_ 1 is as hereinabove described, and Z_- is: (i) R 31 ; di ) R 31 -R 32 ; ( iϋ ) R 31 - 32 - R 32 ; (iv) 31 - R 32 - 32 - R 33 ; (v) R 31 - R 32 - R 32 - 33 - R 31 ; or ( v i ) R 31 - R 32 - R 32 - R 33 - R 3 R 3 2 ' In accordance with yet another embodiment, the peptide may include the following structure: (Y 3lV X 3r CZ 3lV Whβrein Y 31 ^ Z 31 βre aS previously defined, a is 0 or 1, and b is 0 or 1. When the peptide includes the structure X__, the peptide may include the following structure: Y_„ - X__, wherein X_. is as hereinabove described, and Y 32 is: (i) R 31 ; (ii) R 32 -R 31 ; (iii) 32 - R 32 - 31 ; (iv) R 3l 'R 32 "R 32 "R 31 ; (v) R 33 - 31 - 32 - R 32 - 31 ; O - (vi) 32 - 33 - R 31 - 32 - R 32 "R 31- In another embodiment, when the peptide includes the structure X , the peptide may include the following structure: X,_ - Z,_, wherein X,_ is as hereinabove -described, and Z 32 is: (i) R 32 ; (ID R 32 -R 32 ; (iii) R 32 - R 32 -R 33 ; (iv) R 32 " R 32 - R 33 - 31 ; (v) R 32 - 32 - 33 -R 31 - R 32 ; or (vi) R 32 - R 32 - 33 - R 31 - R 32 - 32 - In accordance with yet another embodiment, the peptide may include the following structure: ^32^ ■ X 32 * (Z 32V Wherβin Y 32 ^ Z 32 are βS previously defined, a is 0 or 1, and b is 0 or 1. In accordance with another embodiment, when the peptide includes the structure X- > - j. the peptide may include the following structure: Y__ - X,, wherein X_, is as hereinabove described, and Y 33 is: (i) R 32 ; (ii) R 31 -R 32 ; (iii) R 32 - R 31 - R 32 ; (iv) R 32 -R 32 - R 31 - 32 ; (v) R 3l "R 32 "R 32 "R 3r R 32 ; ° r (vi) 3 3 - 31 - 3 2 - R 32- R 3 R 32' wherein R 3 1> R 32' "^ R _ are as hereinabove described. In accordance with another embodiment, when the peptide includes the structure X.,-,- the peptide may include the following structure: X,, - Z _ wherein X_, is as hereinabove described, and Z_ 3 is: (i) R 32 ; (ii) R 32 -R 33 ; (iii) R 32 - R 33 " R 31 ; ( iv) R 32 - R 33 - 31 - R 32 ; (v) R 32 - R 33 - R 31 - 32 - 32 ; or (vi) R 32 - 33 - R 31 - R 32 - R 32 - 31 - In accordance with yet another embodiment, the peptide may include the following structure: ■ X 33 " (Z 33 } b' Where±n Y 33 *"* Z 33 are βS 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 , , the peptide may include the following structure: Y„, - X_, , wherein X_. is as hereinabove described, 34 34 34 and Y_. is: 34 (i) R 32 ; (ii) R 32 -R 32 ; (iii) R 31 - R 32 - R 32 ; ( iv) 32 - R 31 - 32 - R 32 ; (v) 32 - R 32 - R 31 - R 32 "R 32 ; ° r (vi) 3 32 - R 32 - R 3 R 32 - R 325 wherein R^, R 32 and R are as hereinabove described. In accordance with another embodiment, when the peptide includes the structure X- . the peptide may include the following structure: X 3_4,-Z3_4,, wherein X3_4, is as hereinabove described, and Z_. is: 34 (i) R 33 ; (ii) R 33 -R 31 ; (iii) R 33 - R 31 - 32 ; (iv) 33 - R 31 - R 32 - R 32 ; (v) 33 - R 31 - R 32 - 32 - 31 ; or (vi) 33 - R 31 " R 32 - R 32 - R 31 - 32 - In accordance with yet another embodiment, the peptide may include the following structure: (Y 34V X 3 - (Z 34V Whereln X 34 md Z 34 flre βS 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 _, the peptide may include the following structure: Y is as hereinabove described, and Y 35 is: (i) R 33 ; (ii) R 32 -R 33 ; (iii) 32 - R 32 - R 33 ; ( iv) R 31 - R 32 - R 32 - R 33 ; < V) R 32- R 3 r R 32- R 32 "R 33 ; ° r (vi) 32 - 32 -R 3 R 32 - 32 - R 33 . wherein R 31> R 32 , and R , are as hereinabove described. In accordance with another embodiment, when the peptide includes the structure X,_, the peptide may include the following structure: X_ c - Z_. wherein X__ is as hereinabove described, and Z__ is: (i) R 31 ; (ii) R 31 -R 32 ; (iii) R 31 - R 32 - 32 ; (iv) R 31 - R 32 - R 32 - R 31 ; (v) R 31 - R 32- R 32- R 3 R 32 ; ° r (vi) 31 - 32 - R 32 - R 31 - 32 - 32 ' In accordance with yet another embodiment, the peptide may include the following structure: (Y 35V X 35 (Z 3s Wherein X 35 ∞* Z 35 are βS 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 : , the peptide may Jo include the following structure: Y_, - X_, wherein X_- is as hereinabove described, and Y 3g is: (i) R 31 ; (il) R 33 -R 31 ; (iii) R__-R__-R_- ; (iv) R 32 "R 32 "R 33 "R 31 ; (v) R 31 - 32 - R 32 - 33 - R 31 ; or (vi) 32 - 31 - 32 - 32 - R 33 - 3r wherein R 31> R 32> and R _ are as hereinabove described. In accordance with another embodiment, when the peptide includes the structure X--., the peptide may include the following structure: X J n O_~Z.,_O; > wherein XJ_O, is as hereinabove described, and Z„, is: Jo (i) R 32 ; (ii) 32 -R 32 ; (iii) R 32 - R 32 - R 31 ; (iv) 32 - R 32 - R 31 - R 32 ; (v) R 32 - R 32 - R 31 - R 32 - R 32 ; or (vi) 32 - R 32 - R 31 - 32 - 32 - R 33 ' In accordance with yet another embodiment, the peptide may include the following structure: (Y 36V X 36 i Z 3 β ' 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, 7 , the peptide may includes the structure Y__-X__, wherein X„ is as hereinabove described, and Y,_ is: (l) R 32 ; (ID R 31 -R 32 ; (iii) R 33 - 31 - R 32 ; (iv) R 32 - R 33 - R 31 - R 32 ; (v) or R 32 "R 32 "R 33 ' R 3l 'R 32 ; (vi) R 31 " R 32 " R 3 2 " R 33" R 3i" R 3 ' wherein R 3J , R 32> and R are as hereinabove described. In accordance with a further embodiment, when the peptide includes the structure X__, the peptide may include the following structure: X, 7 - Z__ wherein X, 7 is as hereinabove described, and Z__ is: (i) R 32 ; (ii) R 32 -R 31 ; (iii) R 32 - R 31 - R 32 ; (iv) R 32 - 31 - R 32 - R 32 ; (v) R 32 - R 31 - 32 - R 32 - R 33 ; or (vi) R 32 - R 3 r R 32 'R 32 'R 33 'R 3r In accordance with yet another embodiment, the peptide may include the following structure: (Y 37 ) - X 37 (Z 37 , , wherein Y _ 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 is of one of the following structures as given in the accompanying sequence listing: (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 NO:30). (Lys Phe Ala Gly Lys Phe Ala) 3 (SEQ ID NO:31). (Lys Ala Leu Ser Lys Ala Leu) 3 (SEQ ID NO:32). (Lys Leu Leu Lys Ala Leu Gly) 3 (SEQ ID NO:33). (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 NO: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) (SEQ ID NO:69) In (SEQ ID NO:67) and (SEQ ID NO:68), Xaa is p-aminophenylalanine. In accordance with another embodiment, the amphiphilic peptide includes the following basic structure X, • 40 R 3r R 32 "R 32 'R 33 "R 34 'R 32 "R 32 "R 3r R 32 "R 32 "R 32 "R 34 _R 32 "R 32' wherein -- -J ' and R 3 i are as hereinabove described, and R_ 4 is a basic hydrophilic or hydrophobic amino acid. In accordance with one embodiment, the peptide may include the following structure: Y /n ~X n . wherein X.„ is as hereinabove described, 40 40 40 and Y._ is: 40 (i) R 32 ; (il) R 32 -R 32 ; (iii) R 3A - R 32 - R 32 ; (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 - 33 - 34 - R 32 - 32 . °~ (vii) R 31 -R 32 -R 32 -R 33 -R 34 -R 32 -R 32 ,wherein R 3J ., R 32> 33 34 are as hereinabove described. In accordance with another embodiment, the peptide may include the following structure: X Λ "Z /rι , wherein X,_ is as hereinabove described and 40 40 40 Z 40 1S: (i) R 31 ; (ii) R 31 -R 32 ; (iii) R 31 -R 32 -R 32 ; (iv) 31 - R 32 - R 32 - R 33 ; (v) R 31 - R 32 - R 32 - R 33 - R 3A ; (vi) R 31 - R 32 "R 32- R 33- R 34- R 32 ; or (vii) R 31 - 32 - R 32 - R 33 - R 3A - 3 2 - 32 . wherein R^, R^, R__, and R,, are as hereinabove described. In accordance with yet another embodiment the peptide may include the following structure: (Y 4θY X 4θ "(Z 4θV Wherein Y 40 and Z 40 are βS 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 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) (SEQ ID NO:76) (SEQ ID NO: 7) (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), (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) (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). (SEQ ID NO:90). In accordance with another embodiment, the peptide may be 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: 3) (SEQ ID NO:94) 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. In another embodiment, the amphiphilic peptide includes the following basic structure X cn : R 4 R 42 'R 2 "R 4l 'R 42 "R 42 "R 4 R 4 R 42 'R 4 R 4r 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_ -X c - wherein X_ Λ is as hereinabove described 50 50 50 and Y 50 is: (i) R 41 ; (ii) R 42 -R 41 ; or (iii) R, --R..-R.,, wherein R. - and R._ are as 42 42 41 41. 42 hereinabove described. In one embodiment, R, 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 amphiphilic peptide includes the following basic structure X 52 " R.„-R,.-R,„-R -R 42 41 42 42 41 41 R Λ42 -- R 4.2 -" R Λ4ι1- R 4Λ2 -- R 4/.2 - - wherein R, is a hydrophobic amino acid and R 4 is a basic hydrophilic or neutral hydrophilic amino acid. In one embodiment R. - is leucine. In another 41 embodiment, R,_ is lysine. In one embodiment, the peptide includes the basic structure Y_ -X. , wherein X_ ? is as hereinabove described, and Y_ is: In one embodiment, 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_„ - Z_.„ , wherein X-.,. is as hereinabove described, and Z_. is: (i) R 41 ; ( ii ) 41 - R r (iii) R 41 -R 41 -R 42 ; (v) R 4r R 4l "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 ) β - X 52 - (Z 52 ) b , wherein X^, Y 52 and Z 52 are as 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 X_,: "R 4 R 42 "R 42 "R 4 R R 42 _R 2 "R 4 R 42 "R 42 'R 4 R 4 R 42 'R 42 "R - 43 " ' wherein R. , and R, „ are as hereinabove described, and R. , 41 42 4J 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 cfi : R 4 R 2 'R 4 R 4 R 42 "R 2 "R 4 R 4Γ R 42 'R 42 "R 4 ' wherein R^. and R 4.2_ are as hereinabove described, and R4,4. is a neutral hydrophilic amino acid or proline. In one embodiment, the peptide may include the following structure Y_,-X_,, wherein X c - is the basic JO O O peptide structure hereinabove described, and Y_, is: (i) -R 41 ( ii) - R 41 - R 4 f. ( iii - R A2 - 1 - R A1 ; (I V ) -R 4I -R 42 -R AΓ R ; (v) - R 4 R f R 4 2 "R 4f R 41 ; ( vi ) - 4 2- R 4Γ R 4Γ R 42- R 4Γ R 41 ; or ( vii ) - R 4 2 - R 4 2 - R R 4Γ R Γ R 42 "R 41 "R 41' wherein R4,1, and R4,2„ are as hereinabove described. In one embodiment, the peptide may include the structure: (v) - R 42 "R 42 "R 41- R 4l 'R 42 ; < vl > - R 42 "R 42- R 41- R 4Γ R 42- R 42 ; ° r (vii) - R 42 'R 42 _R 41- R 4r R 42 "R 42 "R 41- In a preferred embodiment, the peptide may have one of the following structures: (SEQ ID NO: 103); or (SEQ ID NO: 104). In another embodiment, the peptide may have the structure (YJ c O,)a-XJ,-,O- . ~(ZJ c O,).D, wherein XJ_O,, YJ r O_ , and ZJ_O, 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 cR : R 4 R 4 R 42 'R 42 'R 4 R 42 "R 42 "R l "R R 42 "R 42 "R 4 R 3' wherein R. , , R, . and R,_ .are as hereinabove described. 41 42 43 In accordance with another embodiment, the peptide may include the structure Y, R -X_ R , wherein X. β is as hereinabove described, and Y CD is: Jo (ii ) - R 42 -R 41 ; ( iϋ ) - 42 - R 42 - R 4 i; ( v ) - R 4 R 4 R 42 . R 42 "R 4i ; (V1) - R 42 'R 4 R 1- R 42- R 2- R 1 ; or ( vii ) - R 42 "R 42 "R 41- R 4 R 42 _R 42 "R 41' wherein Y 41 and R4.2„ are as hereinabove described. In another embodiment, the peptide includes the structure X J_o-Z5-8„, wherein X5 r 8 β is as hereinabove described, and Z_ R is: (i) -R 41 ; ( ϋ - R 41- R 45 : ( iii ) -R 1 - R 45 - R 45; (iv) -R 41 -R 45 -R 45 _R 3 ; (v) -R 41 -R 45 -R 45 _R 43 -R 41 ; (vi) -R 41 -R 45 -R 45 _R 43 -R 41 -R 43 ; (vii) -R 41 -R 45 -R 45 _R 43 -R 41 -R 43 -R 43 , (viii) -R 41 -R 45 -R 45 .R 43 -R 41 -R 43 -R 43 -R 45 ; or (ix) -R 41 -R 45 -R 45 _R 43 -R 41 -R 43 -R 43 -R 45 -R 43 , wherein R4. ,1 and R4,3. are as hereinabove described, and R4,5_ is proline. In one embodiment, the peptide has the following structure: (SEQ ID NO:105). In one embodiment, the peptide may have the structure Z 58 βre βS 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 fin ; R 4 R 4I "R 43 'R 42 'R R 4 R 4 R R 4 R R 2 "R 4 R 4 R 42 "" R 42 "R 4l " R 4 R 42 "R 42 "R 42 "R 41' wherein R 4J , 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 ^n 'Z ^r ,, wherein X-., is as hereinabove oU oU oU described, and Z, n is: OU ( v ) - R 42 - R 42 - R 41 . R 4 r R 42 ; (vi) - R 42 - R 42 - R 41- R 4r R 42- R 42 ; °r ( vii ) - R 42 - R 42 - R 4ι - R 4 R 42 - R 42 - R 4ι - In accordance with yet another embodiment, the peptide has a structure selected from the group consisting of: (a) R 4 R 42 "R 42 "R 4r R 42 "R 42 "R 41 ; (b R 4 R 4r R 42 'R 42 "R 4l "R 42 "R 42 'R 41 ; (c) R 42 "R 4 R 4 R 42 _R 42 *R 4 R 42 "R 42 "R 41 ; (d) R 42 "R 42 "R 41 "R 4 R 42 'R 42 "R 4Γ R 42 'R 42 'R 41 ; βnd (e R 4 R 42 "R 42 "R 4l "R 4r R 42 'R 42 "R 4 R 42 "R 42 'R 4r wherein R, - and R, - are as hereinabove described. 41 42 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. 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 another embodiment, the peptide is elittin. Melittin is an amphipathic peptide consisting of 26 amino acid residues, and is isolated from honeybee (Apis mellifera) venom. The peptide is known to be cytolytic. See Habermann, et al., Hoppe-Seyler's Zeltschrlft Phvsiol. Chem.. Vol. 348, pgs. 37-50 (1987). Melittin has the following structural formula as represented by the three-letter amino acid code: Gly He Gly Ala Val Leu Lys Val Leu 5 Thr Thr Gly Leu Pro Ala Leu He Ser 10 15 Trp He Lys Arg Lys Arg Gin Gin 20 25 (SEQ ID NO: 114) In another embodiment, the peptide purified in accordance with the present invention is an apidaecin. The term apidaecin as used herein includes the basic structure as well as analogues and derivaties thereof. Apidaecins are further described in European Patent Application No. 299,828. In accordance with another embodiment, the peptide may be an amide - or carboxy-terminated peptide represented by the following structural formula, and the numbers below each amino acid residue refer to the position of the residue in the peptide: Leu Lys Leu Leu Lys Lys Leu Leu Lys Lys Leu 1 2 3 4 5 6 7 8 9 10 11 Lys Lys Leu Leu Lys Lys Leu 12 13 14 15 16 17 18 (SEQ ID NO: 115) or the peptide may be an analogue of such peptide wherein at least one of amino acid residues 1 through 7, 9, 11, 12, 14, 16, or 18 is deleted from the peptide. In one embodiment, at least one of amino acid residues 1, 3, 7, 9, 11, 12, 14, 16, or 18 is deleted from the peptide. In other embodiments, amino acid residues 1 through 3, 1 through 4, 1 through 5, 1 through 6, and 1 through 7 are deleted from the peptide. In preferred embodiments, amino acid residues 1 through 3 or 1 through 4 are deleted from the peptide, and such peptides have the following structural formulae: (SEQ ID NO: 116) (SEQ ID NO: 117) In accordance with another embodiment, the peptide includes the following structural formula X-_: O-. R 4 R 4 R 42 "R 4 R r R 42 'R 42 'R 4 R 4l "R 42 "R 42 " R 4 R 42 _R 42 ' wherein R, - is a hydrophobic amino acid, and R,_ is a basic hydrophilic or neutral hydrophilic amino acid. In one embodiment, R, is leucine, and in another embodiment, R, is lysine. In a preferred embodiment, the peptide has the following structure: Leu Leu Lys Leu Leu Lys Lys Leu Leu Lys Lys Leu Lys Lys 5 o (SEQ ID NO: 118) In accordance with another embodiment, the peptide includes the following structural formula X,,: R 42 "R 41 "R 4 R 42 "R 42 'R 4 R 42 "R 42 "R 4 R 4 R 42 "R 42 "R 4l "R 41, wherein R,- is a hydrophobic amino acid, and R,_ is a basic hydrophilic or neutral hydrophilic amino acid. In one embodiment, R 4 is leucine, and in another embodiment, R,. is lysine. In a preferred embodiment, the peptide has the following structural formula: Lys Leu Leu Lys Lys Leu Lys Lys Leu Leu Lys Lys Leu Leu 5 10 (SEQ ID NO:119) In another embodiment, the peptide includes the following structural formula X,,: oo R 4 R 4 R 2 "R 2 "R R 2 'R 2 "R R 4 R 42 "R 42 "R 4l "R r wherein R 4 _ is a hydrophobic amino acid, and R 42 is a basic hydrophilic or neutral hydrophilic amino acid. In one embodiment, the peptide may include the following structure: X β6 -Z, 6 , wherein X , is as hereinabove described and is: J 66 (ii) 42 -R 41 ; or (iii) R 42 -R 41 - R 41 - In one embodiment, R,. is leucine, and in another embodiment, R, 2 is lysine. In a preferred embodiment, the peptide has the following structural formula: Leu Leu Lys Lys Leu Lys Lys Leu Leu Lys Lys Leu Leu Lys 5 10 Leu Leu 15 (SEQ ID NO: 120) In accordance with yet another embodiment, the amphiphilic peptide or protein may be an ion channel-forming peptide or protein. 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, 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, > 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. Exo. 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. The peptides may be produced by known techniques and obtained in substantially pure form. For example, the peptides may be synthesized on an automatic peptide synthesizer. Journal of the American Chemical Society. Vol. 85, pgs. 2149-54 (1963). It is also possible to produce such peptides by genetic engineering techniques. The codons encoding the amino acids 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 transfeet such an expression vehicle into a cell which will express the peptide. Thus, it is contemplated within the scope of the present invention that one may treat a dermatological malignancy by administering transfected cells which include an expression vehicle to a host containing DNA encoding ion channel-forming peρtide(s) or protein(s) such as those hereinabove described. It is also to be understood that the peptides or proteins may be administered in combination with one another. n accor ance w ano er em o men , ne pep e or protein may be administered in combination with an ion having pharmacological properties. An ion having pharmacological properties is one which when introduced into a target cell, inhibits and/or prevents and/or destroys the growth of the target 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 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, active and/or inactive, 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, silver, zinc, mercury, copper, platinum, antimony, gold, nickel, selenium, and bismuth ions. The peptide or protein and 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 .. dermatological malignancy. In effect, the ion potentiates the action of the peptide, i.e., the amount of the ion is effective to reduce the maximum effective concentration of the peptide or protein for inhibiting growth of a dermatological malignancy. The ion having pharmacological properties,. when used systemically (e.g., intravenously, intraperitoneally, intralesionally), is generally employed in an amount of from 1 mg to 10 mg per kg of host weight. Peptide or protein dosages may be within the ranges hereinabove described. The ion may be administered in the form of a salt such as, for example, sodium fluoride. The peptides or proteins may be administered in combination with chemotherapeutic agents such as, but not limited to, cyclophosphamide, cisplatin, dσxorubicin, hexamethylamine, and VP-16. The invention will now be described with respect to the following examples; however, the scope of the present invention is not intended to be limited thereby. Examp1e 1 Melanoma cell lines WM239-A (metastatic melanoma), WM278 (primary melanoma), WM793 (primary melanoma), WM1158 (metastatic melanoma) were seeded in 24-well plates at a concentration of 7.5 x 10 cells/ml containing 2% tumor medium. Peptides (SEQ ID NO: 121), (SEQ ID NO: 122), D-(SEQ ID NO: 121), in which each amino acid residue is a D-amino residue or a glycine residue, and a "control" peptide having the structure of Magainin II (SEQ ID NO:7), in which the Phe and Lys residues are D-amino acid residues, were frozen at -20°C in 100 ml aliquots at a concentration of 25 mg/ml. Each peptide was then dissolved in sterile distilled water at a dilution of 1:1,000 or 1:5,000 to provide peptide concentrations of 25 μg/ml or 5 μg/ml, respectively. The peptides at the 25 μg/ral or 5 μg/ml concentrations were then added to the plates containing the melanoma cells. The amount of 3 H-thymidine incorporation for each well was taken on days 1, 3, and 7. The percentage of growth reduction of each cell line after 7 days by each peptide is given in Table 1 below. Table I Pe p tide Dose % Growth Reduction (7 days) (μ g /ml ) WM239-A WM-278 WM793 WM1158 NO :.!« * ) 5 82.0 25 96.3 Control 5 0 25 0 Example 2 Peptides (SEQ ID NO: 117) and D-(SEQ ID NO: 117), in which each amino acid residue is a D-amino acid residue, are tested for % growth reduction of melanoma cell lines WM852 (grown in 2% tumor media or PF media), WM983A (grown in 2% tumor media or PF media), WM793 (grown in 2% tumor media), and WM1985 (grown in PF media) according to the procedure of Example 1, except that only a concentration of 25 μg/ml was employed for (SEQ ID NO: 117), and concentrations of 1.0, 2.5, 5.0, 10.0, and 25.0 μg/ml were employed for D-(SEQ ID NO: 117). The results are given in Table II below. Table II Pe tide Dose Growth edu t on 7 Example 3 The following melanoma cell lines are seeded in 200 ul of 2.0% 4 tumor medium at a density of 1.5 x 10 cells per well in a 96-well microtitor plate: WM1791A WM35 WM852 WM983A WM1366 WM8 WM115 WM983B WM39 WM1158 SKMel 23 WM164 WM902B WM793; and WM239A. The following day, the media are removed, and solutions of peptides D-(SEQ ID NO: 121) and D-(SEQ ID NO: 117) in 2% tumor media are added in triplicate at the following concentrations: 0 (control) 1.0 μg/ml 5.0 μg/ml 25.0 μg/ml 94/12206 On the next day, lμCi of 3H-thymidine is added to each well. After 18 hours, the medium was discarded, and the cells were detached by addition of 50 ul of trypsin/versene solution. The loose cells were then harvested using a Tomtec cell harvester. The cells were trapped on filters, and the radioactivity quantitated by liquid scintillation counting using a Packard instrument. The radioactive counts for each cell line contacted with the peptides is given in Table III below. It is to be understood, however, that the scope of the present invention is not to be limited to the specific embodiments described above. The invention may be particularly described and still be within the scope of the accompanying claims. SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: Jacob, Leonard S. Maloy, W. Lee (ii) TITLE OF INVENTION: Treatment of Melanoma with Biologically Active Peptides (iii) NUMBER OF SEQUENCES: 122 (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: (B) FILING DATE: (C) CLASSIFICATION: (vii) 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: 421250-209 (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: W0B9/11290 (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: (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 (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: : (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 (x) PUBLICATION INFORMATION: (H) DOCUMENT NUMBER: W089/11290 (I) FILING DATE: 19-MAY-1989 (J) PUBLICATION DATE: 30-NOV-1989 ( i) 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: AUG - 1987 (H) DOCUMENT NUMBER: US 48.10777 (I) FILING DATE: 04-MAR-1987 (J) PUBLICATION DATE: 07-MAR-1989 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: Gly lie 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 (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 (xi) 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 lF) 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: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 (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 (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: ( xi ) SEQUENCE DESCRIPTION : SEQ 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) PUBLICATION INFORMATION: (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 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (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 (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (x) PUBLICATION INFORMATION: (A) AUTHOR: Richter, K (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 (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 ( i) 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: (A) AUTHOR: Richter, K. Egger, R. Kreil (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 3676-3680 (G) DATE: 1986 (A) AUTHOR: Wakabayashi, T. Kato, H. Tachibaba, S. (C) JOURNAL: Nucleic Acids Research (D) VOLUME: 13 (F) PAGES: 1817-1828 ( G ) DATE : 1985 (A) AUTHOR: Gibson, B.W. Poulter, L. Williams, D.H. Maggio, J.E. (C) JOURNAL: J. Biol. Chem. (D) VOLUME: 261 (F) PAGES: 5341-5349 (G) DATE: 1986 (H) DOCUMENT NUMBER: W090/04407 (I) FILING DATE: 16-OCT-1989 (J) PUBLICATION DATE: 03-MAY-1990 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 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 (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. (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18: Gly Phe Ala Ser Phe Leu Gly Lyε Ala Leu 5 ' 10 Lyε 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. (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 (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 (H) DOCUMENT NUMBER: W090/04407 (I) FILING DATE: 16-OCT-1989 (J) PUBLICATION DATE: 03-MAY-1990 (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. (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 fil) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (X) (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 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (x) (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 (G) DATE: 1985 (A) AUTHOR: Gibson, B.W. (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 (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: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (A) NAME/KEY: CPF peptide. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: Gly Leu Ala Ser Leu Leu Gly Lyε Ala Leu 5 10 Lys Ala Ala Leu Lyε 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 acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) 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 (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 lie 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 Lyε 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 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: Lys Leu Ala Gly Lys Leu Ala Lys Leu Ala 5 10 Gly Lyε 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 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: Lys Ala Leu Ser Lys Ala Leu Lyε Ala Leu 5 10 Ser Lyε Ala Leu Lys Ala Leu Ser Lyε Ala 15 20 Leu (2) INFORMATION FOR SEQ ID NO:33: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: Lyε Leu Leu Lyε 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 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: Lys Ala He Gly Lyε Ala He Lyε Ala He 5 10 Gly Lyε Ala He Lyε Ala He Gly Lyε Ala 15 20 He (2) INFORMATION FOR SEQ ID NO:35: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (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 Lyε 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 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: Lys He Ala Lys He Phe Gly Lyε He Ala 5 10 Lyε He Phe Gly Lyε He Ala Lyε 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 (xi) 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 ammo acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) 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 Lyε (2) INFORMATION FOR SEQ ID NO: 40: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa iε ornithine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40: Lys He Ala Gly Xaa He Ala Lyε He Ala 5 10 Gly Xaa He Ala Lyε He Ala Gly Xaa He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:41: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (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 Lyε He Ala 5 10 Arg He Ala Gly Lyε He Ala Arg He Ala 15 20 Gly (2) INFORMATION FOR SEQ ID NO: 42: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (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:42: Xaa He Ala Gly Lyε 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 Lyε Gly He Ala 5 10 Arg He Phe Lyε Gly He Ala Arg He Phe 15 20 Lyε (2) INFORMATION FOR SEQ ID NO:44: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa iε norleucine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: Lys Xaa Ala Gly Lys Xaa Ala Lys Xaa Ala 5 10 Gly Lys Xaa Ala Lyε Xaa Ala Gly Lyε Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO:45: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa iε norleucine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: Lyε 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 (ix) FEATURE: (D) OTHER INFORMATION: Xaa is norleucine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: Lyε He Ala Gly Lyε Xaa Ala Lyε He Ala 5 10 Gly Lyε Xaa Ala Lyε He Ala Gly Lys Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO:47: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 2.1 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa is norvaline. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: Lys Xaa Ala Gly Lys Xaa Ala Lys Xaa Ala 5 10 Gly Lyε Xaa Ala Lyε Xaa Ala Gly Lyε Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO:48: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( ix ) FEATURE : (D) OTHER INFORMATION: Xaa is norvaline. (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 Lyε Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO:49: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: Lyε 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 (ii) MOLECULE TYPE: peptide (xi) 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 norvaline. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51: Lys He Ala Gly Lys Xaa Ala Lyε He Ala 5 10 Gly Lys Xaa Ala Lyε He Ala Gly Lyε 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 (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:52: Hiε He Ala Gly Hiε He Ala Hiε He Ala 5 10 Gly Hiε 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 Lyε He Ala Lys He Ala Gly Lyε 5 10 He Ala Lys He Ala Gly Lys He Ala Lyε 15 20 He (2) INFORMATION FOR SEQ ID NO: 54: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: He Ala Lyε He Ala Gly Lyε He Ala Lys 5 10 He Ala Gly Lyε He Ala Lyε He Ala Gly 15 20 Lyε (2) INFORMATION FOR SEQ ID NO:55: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (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 Lyε He Ala Gly Arg He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:56: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:56: Arg He Ala Gly Arg He Ala Arg He Ala 5 10 Gly Arg He Ala Arg He Ala Gly Arg He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:57-: (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:57: Lyε 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 acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 58: Lyε He Ala Gly Lyε Val Ala Lyε 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 Lyε He Ala Gly Lyε 15 20 He (2) INFORMATION FOR SEQ ID NO:60: (i ) SEQUENCE CHARACTERISTICΞ (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa iε ornithine. (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 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:62: Lyε He Ala Gly Lys Phe Ala Lys He Ala 5 10 Gly Lys Phe Ala Lyε He Ala Gly Lyε 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 Lyε Xaa Ala 5 10 Gly Lyε 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 (ix) FEATURE: (D) OTHER INFORMATION: Xaa iε norleucine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:64: Lyε 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 (xi) 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 (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 iε p-aminophenylalanine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:67: Xaa He Ala Gly Lyε He Ala Xaa He Ala 5 10 Gly Lys He Ala Xaa He Ala Gly Lyε He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:68: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: Xaa iε p-aminophenylalanine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:68: Lyε He Ala Gly Xaa He Ala Lys He Ala 5 10 Gly Xaa He Ala Lyε 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 Lyε He Ala 5 10 Lyε He Ala Gly Lyε He Ala Lyε He Ala 15 20 Gly Lyε He Ala (2) INFORMATION FOR SEQ ID NO:70: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:70: Lyε Leu Ala Ser Lyε Ala Gly Lyε He Ala Gly 5 10 Lys He Ala Lys Val Ala Leu Lyε Ala Leu 15 20 (2) INFORMATION FOR SEQ ID NO: 71: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( iκ) FEATURE : (D) OTHER INFORMATION: Xaa iε ornithine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 71: Lyε He Ala Gly Lyε He Ala Lyε He Ala Gly 5 10 Xaa He Ala Lyε He Ala Gly Lyε 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 (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 (ix) FEATURE: (D) OTHER INFORMATION: Xaa iε 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 norvaline. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74: Lys He Ala Gly Lys He Ala Lyε 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 i « * ornithine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 75: Lyε 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: (D) OTHER INFORMATION: Xaa iε ornithine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 76: Lyε He Ala Gly Lyε Phe Ala Lyε He Ala 5 10 Gly Xaa Phe Ala Lyε He Ala Gly Lyε Phe 15 20 Ala (2) INFORMATION FOR SEQ ID NO: 77: (i) SEQUENCE CHARACTERIS ICS (A) LENGTH: 21 amino acidε (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. (xi) 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 Lyε Xaa 15 20 Ala (2) INFORMATION FOR SEQ ID NO: 78: (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:78: Lys Met Ala Ser Lyε Ala Gly Lyε He Ala 5 10 Gly Lyε He Ala Lyε Val Ala Leu Lyε Ala 15 20 Leu (2) INFORMATION FOR SEQ ID NO: 79: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 79 Lys He Ala Ser Lyε Ala Gly Lyε He Ala 5 10 Gly Lyε He Ala Lyε 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 (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa iε norleucine. (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:80: Lyε He Ala Ser Lyε Ala Gly Lyε Xaa Ala 5 10 Gly Lyε He Ala Lyε Val Ala Leu Lyε 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: Lyε 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 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: Xaa iε norleucine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:82: Lyε Xaa Ala Ser Lyε Ala Gly Lys Xaa Ala 5 10 Gly Lyε He Ala Lyε Val Ala Leu Lyε 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 i ε 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 (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 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:85: Lyε He Ala Gly Lys He Ala Lyε 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 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:86: Lyε He Ala Gly Lyε He Ala Lyε He Ala 5 10 Gly Lyε He Ala Lyε He Ala Gly Ala He 15 20 Ala (2) INFORMATION FOR SEQ ID NO:87: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS:. (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:87: Lyε Leu Ala Ser Lyε Ala Ala Lyε He Ala 5 10 Ala Lyε He Ala Lyε Val Ala Leu Lyε Ala 10 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 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:88: Lys He Ala Lys Lyε He Ala Lys He Ala 5 10 Lys Lys He Ala Lys He Ala Lyε Lys He 15 20 Ala (2) INFORMATION FOR SEQ ID NO: 89: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acidε (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 Lyε Lyε Phe Ala Lyε Phe Ala Lys Lys Phe 15 20 Ala (2) INFORMATION FOR SEQ ID NO: 90: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:90: Lyε Phe Ala Lyε Lyε He Ala Lyε Phe Ala 5 10 Lyε Lyε He Ala Lyε Phe Ala Lyε Lyε He 15 20 Ala (2) INFORMATION FOR SEQ ID NO: 91: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:91: Ala He Ala Gly Lyε He Ala Lyε He Ala 5 10 Gly Lyε He Ala Lyε He Ala Gly Lyε He 15 20 Ala (2) INFORMATION FOR SEQ ID NO: 92: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 21 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (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 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:94: Gly Met Ala Ser Lyε Ala Gly Lyε He Ala 5 10 Gly Lyε He Ala Lyε Val Ala Leu Lyε 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 Lyε Leu Leu Lyε 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 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:96: Leu Leu Lys Lyε Leu Lyε Lyε Leu Leu Lyε 5 10 Leu Leu (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 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:98: Lys Lys Leu Leu Lys Lys Leu Lys Lyε 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 (ii) MOLECULE TYPE: peptide (ix) 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: Lyε Leu Lyε Lyε Leu Leu Lyε Lys Leu Lyε 5 10 Lyε Leu Leu Lyε Leu Leu 15 (2) INFORMATION FOR SEQ ID NO: 101: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 15 amino acidε (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 Lyε 5 10 Leu Leu Lyε Lyε Asn .. 15 (2 ΪNEORMATION 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 homoserine. (xi) SEQUENCE DESCRIPTION: SEQ ID NO:102: Leu Lyε Lyε Leu Leu Lyε Lyε Leu Lyε 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: ammo acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 103: Leu Lys Leu Leu Lys Lyε Leu Leu Lyε Lyε 5 10 Asn Lys Lys Leu Leu Lys Lys Leu 15 (2) INFORMATION FOR SEQ ID NO: 104: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 18 ammo acids (B) TYPE: ammo acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 104: Leu Lys Leu Leu Lyε Lyε 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 acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 105: Leu Leu Lyε Lyε Leu Lys Lyε Leu Leu Lyε 5 10 Lyε 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 am o acids (B) TYPE: ammo acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 106: Leu Ala Ser Lyε Ala Gly Ala He Ala Gly 5 10 Lyε 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 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 107: Leu Lyε Lys Leu Lyε Lyε Leu 5 (2) INFORMATION FOR SEQ ID NO: 108: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 8 ammo acidε (B) TYPE: ammo acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 108: Leu Leu Lyε Lyε Leu Lyε Lys Leu 5 (2) INFORMATION FOR SEQ ID NO: 109: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 9 ammo 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 Lyε Lyε Leu Lyε Lyε Leu 5 10 (2) INFORMATION FOR SEQ ID NO: 111: (i) SEQUENCE CHARACTERISTICS (A) LENGTH: 11 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 111: Leu Lyε Lyε Leu Leu Lyε Lyε Leu Lyε Lyε 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 Lyε Leu Leu Lyε Lyε Leu Lyε 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 Lyε Lyε Leu Leu Lys Lys Leu Lys Lys Leu 5 10 Leu Lyε Arg (2) INFORMATION FOR SEQ ID NO: 114: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 26 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) ORIGINAL SOURCE (A) ORGANISM: Apis mellifera ( vii ) FEATURE (A) NAME/KEY: melittin peptide (X) PUBLICATION INFORMATION: (A) AUTHORS: Habermann, E. Jentsch, J. (B) TITLE: Seguenzanalyse des Melittins aus den tryptischen and peptischen Spaltstucken (C) JOURNAL: Hoppe-Seyler* s Zeitschrift Phyεiol. Chem. (D) VOLUME: 348 (F) PAGES: 37-50 (G) DATE: 1987 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 114: Gly He Gly Ala Val Leu Lyε Val Leu 5 Thr Thr Gly Leu Pro Ala Leu He Ser Trp 10 15 He Lys Arg Lys Arg Gin Gin 20 25 (2) INFORMATION FOR SEQ ID NO: 115: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 115: Leu Lys Leu Leu Lys Lys Leu Leu Lys Lys 5 10 Leu Lys Lys Leu Leu Lys Lys Leu 15 (2) INFORMATION FOR SEQ ID NO: 116: (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: C-terminal amide, may be acetylated at N-terminus. (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 116: Leu Lys Lys Leu Leu Lys Lys Leu Lyε Lys 5 10 Leu Leu Lys Lys Leu 15 (2) INFORMATION FOR SEQ ID NO: 117: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 14 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: (D) OTHER INFORMATION: C-terminal amide, may be acetylated at N-terminuε. (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 117: Lys Lyε Leu Leu Lys Lys Leu Lys Lys Leu 5 10 Leu Lys Lys Leu (2) INFORMATION FOR SEQ ID NO: 118: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 14 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 118: Leu Leu Lys Leu Leu Lyε Lyε Leu Leu Lyε 5 10 Lyε Leu Lyε Lyε (2) INFORMATION FOR SEQ ID NO: 119: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 14 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 119: Lyε Leu Leu Lyε Lyε Leu Lyε Lyε Leu Leu 5 10 Lyε Lyε Leu Leu (2) INFORMATION FOR SEQ ID NO: 120: (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: 120: Leu Leu Lyε Lys Leu Lys Lyε Leu Leu Lyε 5 10 Lys Leu Leu Lys Leu Leu 15 (2) INFORMATION FOR SEQ ID NO: 121: (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: 121: Gly He Gly Lys Phe Leu Lys Ser Ala Lyε 5 10 Lyε Phe Gly Lyε Ala Phe Val Lyε He Leu 15 20 Asn Ser (2) INFORMATION FOR SEQ ID NO: 122: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 amino acidε (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 122: Gly He Gly Lys Phe Leu Lys Lys Ala Lys 5 10 Lys Phe Ala Lys Ala Phe Val Lys He He 15 20 sn Asn

Claims: WHAT IS CLAIMED IS: 1. A process for treating a dermatological malignancy in a host, comprising: administering to a host at least one biologically active amphiphilic ion channel-forming peptide or protein, said peptide or protein being administered in an amount effective to treat a dermatological malignancy in a host. 2. The process of Claim 1 wherein said peptide or protein is selected from the group consisting of: (a) magainin peptides; (b) PGLa peptides; (c) XPF peptides; (d) CPF peptides; (e) cecropins; (f) sarcotoxins; (g) a peptide including one of the following basic structureε X_. through X 37 wherein: X. k 31 is -[R 31 -R 32 -R 32 -R 33 -R 31 -R 32 -R 32 C 32 is ~ [ R 32~ R 32~ R 33~ R 31~ R 32~ R 32~ R 31 C 33 iS "fR 32 "R 33~ R 31~ R 32 "R 32~ R 3l "R 32 C 34 is ~ IR 33 "R 31~ R 32 "R 32~ R 31 "R 32 "R 32 35 is -[R 31 -R 32 -R 32 -R 31 -R 32 -R 32 -R 33 C 36 is -[R 32 -R 32 -R 31 -R 32 -R 32 -R 33 -R 31 and X 37 is "tR 32 "R 3l "R 32 "R 32 "R 33~ R 3l "R 32 wherein R 31 iε a basic hydrophilic amino acid, R_ 2 is a hydrophobic amino acid, R__ is a neutral hydrophilic, basic hydrophilic, or hydrophobic amino acid, and n is from 2 to 5; (h) a peptide including the following basic structure X 4Q : R 31~ R 32 "R 32 "R 33~ R 33 "R 32 "R 32 "R 3i "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 3 _ is a neutral hydrophilic or hydrophobic amino acid, and R_ 4 is a basic hydrophilic or hydrophobic amino acid; (i) a peptide including the following basic structure X 5 -. 94/12206 R 41- R 42- R 42- R 41- R 42~ R 42- R 41- R 41- R 42- R 41- R 1-' wherein R 4 1 is a hydrophobic amino acid, and R- 2 is a basic hydrophilic or neutral hydrophobic amino acid; (j) a peptide including the following basic structure X j --,: R 2- R 41- R 42- R 42 "R 4 R 4r R 42- R 42- R 4l "R 42~ R 42-' wherein R 4 1 is a hydrophobic amino acid, and R 42 is a basic hydrophilic or neutral hydrophilic amino acid; (k) a peptide including the following basic structure X 54 "R 41~ R 42~ R 42 "R 4l "R 4l "R 42 "R 42~ R 4l "R 42~ R 42 "R 41~ R 4l " R 42~ R 42~ R 43~' wherein R 4i s a hydrophobic amino acid, R 42 is a basic hydrophilic or neutral hydrophilic amino acid, and R._ is neutral hydrophilic amino acid; (1) a peptide including the following basic structure X 3 c D, -. "R 4r R 42~ R 4l "R 41~ R 42~ R 42 "R 41~ R 4l "R 42~ R 42~ R 44 " ' wherβin R 4 ι 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; (m) a peptide including the following basic structure X 58 : "R 4l "R 4l "R 42 'R 42 "R 4l "R 42 "R 42 "R 4l "R 4l "R 42~ R 42~ R 4l "R 43' wherein R 41 is a hydrophobic amino acid, R 4 _ is a basic hydrophilic or neutral hydrophilic amino acid, and R 4.o- is a neutral hydrophilic amino acid; (n) a peptide including the following basic structure Xo-.,U_.: "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 4l "R 4l" R 42~ R 42~ R 42~ R 41' wherein R 4 i is a hy d ropho b ic amino acid, R 42 is a basic hydrophilic or neutral hydrophilic amino acid, and R 43 is a neutral hydrophilic amino acid; (o) a peptide having a structure selected from the group consisting of: (i) R 4 ι- R 42 _R 42 "R 41 "R 42 "R 42 'R 41 ; ( ii ) R 41 -R 41 -R 42 - R 42 "R 4 l- R 4 2 "R 42 "R 41 ' ( iii ) R 42 - R 4i- R 4i- R 42- R 2 "R 4l "R 42 "R 42 "R 41 ; (iv) R 42 " 42~ R 41~ R 41~ R 42~ R 42~ R 4l "R 42 "R 42~ R 41' anC ^ ( v ) R 41 -R 42 -R 42 -R 41 -R 41 -R 42 -R 42 -R 41 -R 42 -R 42 -R 4 wherein R 41 iε a hydrophobic amino acid, and R 42 ± a a basic hydrophilic amino acid or a neutral hydrophilic amino acid; (p) a peptide, said peptide being an amide - or carboxy-terminated peptide represented by the following structural formula, and the numbers below each amino acid residue refer to the position of the residue in the peptide: Leu Lys Leu Leu Lys Lys Leu Leu Lys Lys Leu 1 2 3 4 5 6 7 8 9 10 11 Lys Lys Leu Leu Lys Lys Leu 12 13 14 15 16 17 18 or an analogue of said peptide wherein at least one of amino acid residues 1 through 7, 9, 11, 12, 14, 16 or 18 is deleted from the peptide; (q) a peptide including the following structural formula R 4l "R 4l "R 42 -R 4l "R 4l "R 42 "R 42 "R 4l "R 4l "R 42 "R 42 "R 4l "R 42 "R 42' wherein R.- is a hydrophobic amino acid, and R 4 ~ iε a basic hydrophilic or neutral hydrophilic amino acid; (r) a peptide including the following structural formula 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 4l "R 41' wherein R 41 is a hydrophobic amino acid, and R 42 is a basic hydrophilic or neutral hydrophilic amino acid; (ε) a peptide including the following structural formula R 4l "R 4l "R 42 "R 42 "R 4l "R 42 "R 42 "R 4l "R 4l " R 42 "R 42 "R 4l "R 41' wherein R 4 _, is a hydrophobic amino acid, and R 42 is a basic hydrophilic or neutral hydrophilic amino acid; (t) melittin; (u) apidaecins; (v) defensins; (w) major basic protein of eosinophils; (x) bacterial permeability-increasing protein; and (y) perforin. 3. The process of Claim 2 wherein the peptide is a magainin peptide. 4. The process of Claim 2 wherein the peptide is a PGLa peptide. 94/12206 5 . The process of Claim 2 wherein the peptide is an XPF peptide. 6. The process of Claim 2 wherein the peptide is a CPF peptide. 7. The process of Claim 2 wherein the peptide is a cecropin. 8. The process of Claim 2 wherein the peptide is a sarcotoxin. 9. The process of Claim 2 wherein the peptide includes one of the following basic structures X-., through X-, 7. wherein: \31 is "tR 3l 'R 32 "R 32 "R 33 "R 31~ R 32 "R 32 C 32 is -[R 32 -R 32 -R 33 -R 31 -R 32 -R 32 -R 31 33 is -[R 32 -R 33 -R 31 -R 32 -R 32 -R 31 -R 32 34 1S "tR 33 "R 31~ R 32 "R 32 "R 3l "R 32 "R 32 35 is ~ [R 31~ R 32~ R 32~ R 31~ R 32~ R 32~ R 33 36 is ~^ R 32 "R 32 "R 3l "R 32~ R 32~ R 33 "R 31 and 37 1S ~ [R 32~ R 3l "R 32 "R 32~ R 33 "R 3l "R 32 wherein R 31 s a basic hydrophilic amino acid, R 32 is a hydrophobic amino acid, R 33 is a neutral hydrophilic, basic hydrophilic, or hydrophobic amino acid, and n is from 2 to 5. 10. The process of Claim 2 wherein the peptide includes the following basic structure X 0 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-- is a hydrophobic amino acid, R_ 3 is a neutral hydrophilic or hydrophobic amino acid, and R_ 4 is a basic hydrophilic or hydrophobic amino acid. 11. The process of Claim 2 wherein said peptide includes the following basic structure X ς0 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. 12. The process of Claim 2 wherein said peptide includes the following basic structure ς? : R 42 "R 4l "R 42 "R 42 "R 4l " R 4l "R 42 "R 42 "R 4l "R 42 "R 42' 94/12206 wherein R.. is a hydrophobic amino acid, and R 4? is a basic hydrophilic or neutral hydrophilic amino acid. 13. The process of Claim 2 wherein the peptide includes the following basic structure 54 : "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 4 - iε a hydrophobic amino acid, R 42 is a basic hydrophilic or neutral hydrophilic amino acid, and R._ is a neutral hydrophilic amino acid. 14. The process of Claim 2 wherein the peptide includes the following basic structure X D c O,.: -R 41 -R 42 -R 41 -R 41 -R 42 -R 42 -R 41 -R 41 -R 42 -R 42 -R 44 -, wherein R 41 is a hydrophobic amino acid, R 4? is a basic hydrophilic or neutral hydrophilic amino acid, and R 44 is a neutral hydrophilic amino acid or proline. 15. The process of Claim 2 wherein the peptide includes the following basic structure X ςΘ : -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 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. 16. The process of Claim 2 wherein the peptide includes the following basic structure X β _: "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 4l " ~ R 41~ R 4 2 "" R 4 2~ R 4 2 ~ 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. 17. The process of Claim 2 wherein the peptide has a structure selected from the group consisting of: ( i ) R 4l "R 42 "R 42 "R 4l "R 42 "R 42 "R 41 ' ( ii ) R 4l "R 4l "R 42 "R 42 "R 4 R 42 "R 42 "R 41 ; ( iii ) R 42 "R 4r R 4 R 42 ~ R 42 "R 41~ R 42~ R 42 "R 41 ; ( iv ) R 42~ R 42~ R 4l "R 41~ R 42~ R 42~ R 4l ""R 42~ R 42 "R 41 and ( v ) R 4l "R 42 "R 42 "R 4r R 4r R 42 "R 42 "R 4l "R 42 "R 42 "R 41' wherein R 41 is a hydrophobic amino acid, and R 42 is a basic hydrophilic amino acid or a neutral hydrophilic amino acid. • • 18. The process of Claim 2 wherein said peptide is an amide - or carboxy-terminated peptide represented by the following structural formula, and the numbers below each amino acid residue refer to the position of the residue in the peptide: Leu Lys Leu Leu Lys Lys Leu Leu Lyε Lys Leu 1 2 3 4 5 6 7 8 9 10 11 Lys Lys Leu Leu Lys Lys Leu 12 13 14 15 16 17 18 or an analogue of said peptide wherein at least one of amino acid residues 1 through 7, 9, 11, 12, 14, 16, or 18 is deleted from the peptide. 19. The process of Claim 2 wherein said peptide includes the following structural formula X β2 : R 4l "R 4l 'R 42 ""R 4l "R 4l "R 42 "R 42 "R 4l "R 4l "R 42 "R 42 "R 4l "R 42 "R 42' wherein R 41 is a hydrophobic amino acid, and R 47 is a basic hydrophilic or neutral hydrophilic amino acid. 20. The process of Claim 2 wherein said peptide includes the following structural formula β4 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 41~ R 41' wherein R 41 iε a hydrophobic amino acid, and R 42 is a basic hydrophilic or neutral hydrophilic amino acid. 21. The process of Claim 2 wherein said peptide includes the following structural formula X ββ R 4l 'R 4l "R 42 "R 42 "R 4l "R 42 "R 42 "R 4l "R 4l "R 42 "R 42 "R 4l "R 41' wherein R 41 is a hydrophobic amino acid, and R 4 ~ is a basic hydrophilic or neutral hydrophilic amino acid. 22. The process of Claim 2 wherein said peptide is melittin. 23. The process of Claim 2 wherein said peptide is an apidaecin. 24. The process of Claim 2 wherein said peptide or protein is a defensin. 25. The process of Claim 2 wherein said peptide or protein is major basic protein of eosinophils. 26. The process of Claim 2 wherein said peptide or protein is bacterial permeability-increasing protein. 27. The procesε of Claim 2 wherein εaid peptide or protein is perforin. 28. The process of Claim 2 wherein the peptide iε adminiεtered intralesionally. 29. A process for treating a dermatological malignancy in a host, comprising: administering to a host cells transformed with an expression vehicle including DNA encoding at least one biologically active amphiphilic ion channel-forming peptide or protein, said cells being adminsitered in an amount effective to treat a dermatological malignancy in a host. 30. The process .of Claim 1 wherein said dermatological malignancy is melanoma.

Inventors: JACOB LEONARD S, MALOY W LEE, JACOB, LEONARD, S., MALOY, W., LEE
Applicants: MAGAININ PHARMA, MAGAININ PHARMACEUTICALS, INC.
Application year: 1993
Main classification: A61K37
IPC codes: A61K38, A61P17, A61P35, C07K7, C07K14