Peptides and methods for inducing cell death

Abstract

The invention provide isolated peptides, protides and conjugates having novel peptide sequences which are able to induce antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. The invention also provides a method of inducing programmed cell death in a cell by contacting the cell with an isolated peptide, protide or conjugate described herein. In some aspects, the method can be used in the diagnosis, prevention, or treatment of a disease, such as an infection, cancer, autoimmune disease, or inflammatory disease.

What is claimed is: 
     
         1 . An isolated peptide comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 3, 4, 6, 8, 10, 11, 13, 17, 18, 19, 21-25, 30, 31-36, 39-47, 49-52, 54-57, 59-63, 66-75, 84-93, 102-106, 108-121, 132-175, 179-187, 191-199, 205-209, 211-223, 227-235, 238-243, 245-247, 249-251, 253-256 and 260-263, wherein the amino acid residue represented by (x) is a serine, a threonine, a tryptophan, a H-bond donor residue or a H-bond acceptor residue, wherein the amino acid residue represented by (b) is a lysine, an arginine, an asparagine, a glutamine or a basic residue, wherein the amino acid residue represented by (j) is a cysteine or a thiol residue, wherein in the amino acid residue represented by (o) is an anthrylalanine or other non-natural amino acid and wherein said peptide induces antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. 
     
     
         2 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 3, 4, 6, 8, 10, 11, 13, 264, 270 and 271. 
     
     
         3 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 17, 18, 19, 21-25, 269 and 272. 
     
     
         4 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 30, 31-36 and 273. 
     
     
         5 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 39-47. 
     
     
         6 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 49-52. 
     
     
         7 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 54-57. 
     
     
         8 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 59-63 and 274. 
     
     
         9 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 66-75. 
     
     
         10 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 84-93 and 275. 
     
     
         11 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 102-106, 108-121, 267, 276 and 277. 
     
     
         12 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 132-175. 
     
     
         13 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 179-187, 266 and 278. 
     
     
         14 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NO: 191-199. 
     
     
         15 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 205-209 and 211-223. 
     
     
         16 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 227-235. 
     
     
         17 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 238-243, 245-247, 265 and 279. 
     
     
         18 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 249-251. 
     
     
         19 . The isolated protein of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 253-256. 
     
     
         20 . The isolated peptide of  claim 1  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 260-263 and 268. 
     
     
         21 . An isolated peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 2, 5, 7, 9, 12, 14-16, 20, 26-29, 37, 38, 48, 53, 58, 64, 65, 72, 76-83, 94-101, 107, 114, 122-131, 170, 176-178, 188-190, 200-204, 210, 224-226, 236, 237, 244, 248, 252, 257-259 and 288-289, wherein said peptide induces antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. 
     
     
         22 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 2, 5, 7, 9 and 12. 
     
     
         23 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 14-16 and 20. 
     
     
         24 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 26-29. 
     
     
         25 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from SEQ ID NOS: 37 or 38. 
     
     
         26 . The isolated peptide of  claim 21  consisting of an amino acid sequence of SEQ ID NO: 48. 
     
     
         27 . The isolated peptide of  claim 21  consisting of an amino acid sequence of SEQ ID NO: 53. 
     
     
         28 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from SEQ ID NOS: 58 or 64. 
     
     
         29 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 65 or 72. 
     
     
         30 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 76-83. 
     
     
         31 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 94-101, 107 and 114. 
     
     
         32 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 122-131 and 170. 
     
     
         33 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 176-178. 
     
     
         34 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 188-190. 
     
     
         35 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 200-204 and 210. 
     
     
         36 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 224-226. 
     
     
         37 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 236, 237 and 244. 
     
     
         38 . The isolated peptide of  claim 21  consisting of an amino acid sequence of SEQ ID NO: 248. 
     
     
         39 . The isolated peptide of  claim 21  consisting of an amino acid sequence of SEQ ID NO: 252. 
     
     
         40 . The isolated peptide of  claim 21  consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 257-259 and 288-289. 
     
     
         41 . The isolated peptide of any one of  claims 1 - 40 , wherein the C-terminus of the peptide comprises a carboxamide. 
     
     
         42 . A context-activated protide comprising at least one activator site and two or more effectors, wherein at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 3, 4, 6, 8, 10, 11, 13, 17, 18, 19, 21-25, 30, 31-36, 39-47, 49-52, 54-57, 59-63, 66-75, 84-93, 102-106, 108-121, 132-175, 179-187, 191-199, 205-209, 211-223, 227-235, 238-243, 245-247, 249-251, 253-256 and 260-263, wherein the amino acid residue represented by (x) is a serine, a threonine, a tryptophan, a H-bond donor residue or a H-bond acceptor residue, wherein the amino acid residue represented by (b) is a lysine, an arginine, an asparagine, a glutamine or a basic residue, wherein the amino acid residue represented by (j) is a cysteine or a thiol residue, wherein the amino acid residue represented by (o) is an anthrylalanine or other non-natural amino acid and wherein said at least one effector induces antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. 
     
     
         43 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 3, 4, 6, 8, 10, 11, 13, 264, 270 and 271. 
     
     
         44 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 17, 18, 19, 21-25, 269 and 272. 
     
     
         45 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 30, 31-36 and 273. 
     
     
         46 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 39-47. 
     
     
         47 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 49-52. 
     
     
         48 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 54-57. 
     
     
         49 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 59-63 and 274. 
     
     
         50 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 66-75. 
     
     
         51 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 84-93 and 275. 
     
     
         52 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 102-106, 108-121, 267, 276 and 277. 
     
     
         53 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 132-175. 
     
     
         54 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 179-187, 266 and 278. 
     
     
         55 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NO: 191-199. 
     
     
         56 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 205-209 and 211-223. 
     
     
         57 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 227-235. 
     
     
         58 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 238-243, 245-247, 265 and 279. 
     
     
         59 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 249-251. 
     
     
         60 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 253-256. 
     
     
         61 . The protide of  claim 42  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 260-263 and 268. 
     
     
         62 . A context-activated protide comprising at least one activator site and two or more effectors, wherein at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 2, 5, 7, 9, 12, 14-16, 20, 26-29, 37, 38, 48, 53, 58, 64, 65, 72, 76-83, 94-101, 107, 114, 122-131, 170, 176-178, 188-190, 200-204, 210, 224-226, 236, 237, 244, 248, 252, 257-259 and 288-289, wherein said at least one effector induces antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. 
     
     
         63 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 2, 5, 7, 9 and 12. 
     
     
         64 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 14-16 and 20. 
     
     
         65 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 26-29. 
     
     
         66 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from SEQ ID NOS: 37 or 38. 
     
     
         67 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence of SEQ ID NO: 48. 
     
     
         68 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence of SEQ ID NO: 53. 
     
     
         69 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from SEQ ID NOS: 58 or 64. 
     
     
         70 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 65 or 72. 
     
     
         71 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 76-83. 
     
     
         72 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 94-101, 107 and 114. 
     
     
         73 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 122-131 and 170. 
     
     
         74 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 176-178. 
     
     
         75 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 188-190. 
     
     
         76 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 200-204 and 210. 
     
     
         77 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 224-226. 
     
     
         78 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 236, 237 and 244. 
     
     
         79 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence of SEQ ID NO: 248. 
     
     
         80 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence of SEQ ID NO: 252. 
     
     
         81 . The protide of  claim 62 , wherein said at least one effector comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 257-259 and 288-289. 
     
     
         82 . The protide of any one of  claims 42 - 81 , wherein said activator site is context-activated. 
     
     
         83 . The protide of any one of  claims 42 - 81 , wherein context-activation initiates programmed cell death. 
     
     
         84 . The protide of any one of  claims 42 - 81 , wherein said context-activation results from a physiological condition. 
     
     
         85 . The protide of  claim 84 , wherein said physiological condition is selected from the group consisting of acidity, alkalinity, ionic strength and osmotic strength. 
     
     
         86 . The protide of any one of  claims 42 - 81 , wherein said context-activation results from association with an activator molecule. 
     
     
         87 . The protide of  claim 86 , wherein said activator molecule modifies said activator site upon association. 
     
     
         88 . The protide of  claim 87 , wherein said modification comprises cleavage of said activator site. 
     
     
         89 . The protide of  claim 86 , wherein said activator molecule is an enzyme. 
     
     
         90 . The protide of  claim 89 , wherein said activator molecule is selected from the group consisting of protease, esterase and lipase. 
     
     
         91 . The protide of  claim 90 , wherein said activator molecule is a protease. 
     
     
         92 . The protide of  claim 91 , wherein said activator is expressed by a pathogenic microorganism. 
     
     
         93 . The protide of  claim 92 , wherein said pathogenic microorganism is  Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Bacillus subtilis, Acinotobacter baumannii, Acinotobacter calcoaceticus, Acinotobacter haemolyticus  or  Candida albicans.    
     
     
         94 . The protide of  claim 86 , wherein said activator is present in the context of tumor cells. 
     
     
         95 . The protide of  claim 94 , wherein said activator is a tumor-specific protease. 
     
     
         96 . The protide of  claim 95 , wherein said tumor-specific protease is matrix bound. 
     
     
         97 . The protide of  claim 96 , wherein said tumor-specific protease is a matrix metalloproteinase. 
     
     
         98 . The protide of  claim 86 , wherein said activator is present in the context of an inflammatory response. 
     
     
         99 . The protide of  claim 86 , wherein said activator is a peptide selected from the group consisting of thrombin, bradykinin, elastase and metalloproteinase. 
     
     
         100 . A conjugate comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 3, 4, 6, 8, 10, 11, 13, 17, 18, 19, 21-25, 30, 31-36, 39-47, 49-52, 54-57, 59-63, 66-75, 84-93, 102-106, 108-121, 132-175, 179-187, 191-199, 205-209, 211-223, 227-235, 238-243, 245-247, 249-251, 253-256 and 260-263 and a moiety, wherein the amino acid residue represented by (x) is a serine, a threonine, a tryptophan, a H-bond donor residue or a H-bond acceptor residue, wherein the amino acid residue represented by (b) is a lysine, an arginine, an asparagine, a glutamine or a basic residue, wherein the amino acid residue represented by (j) is a cysteine or a thiol residue, wherein in the amino acid residue represented by (o) is an anthrylalanine or other non-natural amino acid and wherein said conjugate induces antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. 
     
     
         101 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 3, 4, 6, 8, 10, 11, 13, 264, 270 and 271. 
     
     
         102 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 17, 18, 19, 21-25, 269 and 272. 
     
     
         103 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 30, 31-36 and 273. 
     
     
         104 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 39-47. 
     
     
         105 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 49-52. 
     
     
         106 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 54-57. 
     
     
         107 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 59-63 and 274. 
     
     
         108 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 66-75. 
     
     
         109 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 84-93 and 275. 
     
     
         110 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 102-106, 108-121, 267, 276 and 277. 
     
     
         111 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 132-175. 
     
     
         112 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 179-187, 266 and 278. 
     
     
         113 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NO: 191-199. 
     
     
         114 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 205-209 and 211-223. 
     
     
         115 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 227-235. 
     
     
         116 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 238-243, 245-247, 265 and 279. 
     
     
         117 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 249-251. 
     
     
         118 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 253-256. 
     
     
         119 . The conjugate of  claim 100  comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 260-263 and 268. 
     
     
         120 . A conjugate comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 2, 5, 7, 9, 12, 14-16, 20, 26-29, 37, 38, 48, 53, 58, 64, 65, 72, 76-83, 94-101, 107, 114, 122-131, 170, 176-178, 188-190, 200-204, 210, 224-226, 236, 237, 244, 248, 252, 257-259 and 288-289 and a moiety, wherein said conjugate induces antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. 
     
     
         121 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 2, 5, 7, 9 and 12. 
     
     
         122 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 14-16 and 20. 
     
     
         123 . The conjugate of  claim 120  comprising of an amino acid sequence selected from the group consisting of SEQ ID NOS: 26-29. 
     
     
         124 . The conjugate of  claim 120  comprising an amino acid sequence selected from SEQ ID NOS: 37 or 38. 
     
     
         125 . The conjugate of  claim 120  comprising an amino acid sequence of SEQ ID NO: 48. 
     
     
         126 . The conjugate of  claim 120  comprising an amino acid sequence of SEQ ID NO: 53. 
     
     
         127 . The conjugate of  claim 120  comprising an amino acid sequence selected from SEQ ID NOS: 58 or 64. 
     
     
         128 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 65 or 72. 
     
     
         129 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 76-83. 
     
     
         130 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 94-101, 107 and 114. 
     
     
         131 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 122-131 and 170. 
     
     
         132 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 176-178. 
     
     
         133 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 188-190. 
     
     
         134 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 200-204 and 210. 
     
     
         135 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 224-226. 
     
     
         136 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 236, 237 and 244. 
     
     
         137 . The conjugate of  claim 120  comprising an amino acid sequence of SEQ ID NO: 248. 
     
     
         138 . The conjugate of  claim 120  comprising an amino acid sequence of SEQ ID NO: 252. 
     
     
         139 . The conjugate of  claim 120  comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 257-259 and 288-289. 
     
     
         140 . The conjugate of any one of  claims 100 - 139 , wherein said moiety comprises a therapeutic agent, a targeting peptide or a label. 
     
     
         141 . The conjugate of  claim 140 , wherein said therapeutic agent is a cytotoxic agent. 
     
     
         142 . The conjugate of  claim 141 , wherein said cytotoxic agent is an antibiotic. 
     
     
         143 . The conjugate of  claim 140 , wherein said therapeutic agent is a chemotherapeutic agent. 
     
     
         144 . The conjugate of  claim 140 , wherein said targeting peptide selectively homes said conjugate to a microorganism. 
     
     
         145 . The conjugate of  claim 140 , wherein said targeting peptide selectively homes said conjugate to tumor tissue, tumor cell, or tumor vasculature. 
     
     
         146 . The conjugate of  claim 140 , wherein said targeting peptide selectively homes said conjugate to an immune regulatory cell or an immune effector cell. 
     
     
         147 . The conjugate of  claim 140 , wherein said targeting peptide is an antibody or a fragment thereof. 
     
     
         148 . The conjugate of  claim 140 , wherein said label is a radioisotope. 
     
     
         149 . The conjugate of  claim 140 , wherein said label is a dye. 
     
     
         150 . A method of inducing programmed cell death in a cell, comprising contacting said cell with the isolated peptide of any one of  claims 1 - 40 . 
     
     
         151 . The method of  claim 150 , wherein said cell is a microorganism. 
     
     
         152 . The method of  claim 151 , wherein said microorganism is a pathogenic microorganism. 
     
     
         153 . The method of  claim 152 , wherein said pathogenic microorganism is selected from the group consisting of  Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Bacillus subtilis, Acinotobacter baumannii, Acinotobacter calcoaceticus, Acinotobacter haemolyticus, Pseudomonas aeruginosa  and  Candida albicans.    
     
     
         154 . The method of  claim 150 , wherein said cell is a tumor cell. 
     
     
         155 . The method of  claim 154 , wherein said tumor cell is a malignant tumor cell. 
     
     
         156 . The method of  claim 150 , wherein said cell is an immune regulatory cell or an immune effector cell. 
     
     
         157 . A method of inducing programmed cell death in a cell, comprising contacting said cell with the protide of any one of  claims 62 - 81 . 
     
     
         158 . The method of  claim 157 , wherein said cell is a microorganism. 
     
     
         159 . The method of  claim 158 , wherein said microorganism is a pathogenic microorganism. 
     
     
         160 . The method of  claim 159 , wherein said pathogenic microorganism is selected from the group consisting of  Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Bacillus subtilis, Acinotobacter baumannii, Acinotobacter calcoaceticus, Acinotobacter haemolyticus, Pseudomonas aeruginosa  and  Candida albicans.    
     
     
         161 . The method of  claim 157 , wherein said cell is a tumor cell. 
     
     
         162 . The method of  claim 161 , wherein said tumor cell is a malignant tumor cell. 
     
     
         163 . The method of  claim 157 , wherein said cell is an immune regulatory cell or an immune effector cell. 
     
     
         164 . A method of inducing programmed cell death in a cell, comprising contacting said cell with the conjugate of any one of  claims 100 - 139 . 
     
     
         165 . The method of  claim 164 , wherein said cell is a microorganism. 
     
     
         166 . The method of  claim 165 , wherein said microorganism is a pathogenic microorganism. 
     
     
         167 . The method of  claim 166 , wherein said pathogenic microorganism is selected from the group consisting of  Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Bacillus subtilis, Acinotobacter baumannii, Acinotobacter calcoaceticus, Acinotobacter haemolyticus, Pseudomonas aeruginosa  and  Candida albicans.    
     
     
         168 . The method of  claim 164 , wherein said cell is a tumor cell. 
     
     
         169 . The method of  claim 168 , wherein said tumor cell is a malignant tumor cell. 
     
     
         170 . The method of  claim 164 , wherein said cell is an immune regulatory cell or an immune effector cell.