APAP, a sequence-pattern recognition approach identifies substance P as a potential apoptotic peptide.
We have previously described a novel cancer chemotherapeutic approach based on the induction of apoptosis in targeted cells by homing pro-apoptotic peptides. In order to improve this approach we developed a computational method (approach for detecting potential apoptotic peptides, APAP) to detect short PAPs, based on the prediction of the helical content of peptides, the hydrophobic moment, and the isoelectric point. PAPs are toxic against bacteria and mitochondria, but not against mammalian cells when applied extracellularly. Among other peptides, substance P was identified as a PAP and subsequently demonstrated to be a pro-apoptotic peptide experimentally. APAP thus provides a method to detect and ultimately improve pro-apoptotic peptides for chemotherapy.
del Rio
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Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945-1400, USA.
Castro-Obregon
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S
Rao
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Ellerby
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HM
Bredesen
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DE
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology / Q000379:methods*; D019992:Databases as Topic; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007526:Isoelectric Point; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D010363:Pattern Recognition, Automated; D017433:Protein Structure, Secondary; D051381:Rats; D012984:Software; D013373:Substance P / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D013373:Substance P; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases