title: Design, synthesis and biological evaluation of novel peptides with anti-cancer and drug resistance-reversing activities.
abstract: Chemotherapy is an important approach used to treat cancer, but severe side effects and emerging drug resistance restrict its clinical application. In this present study, we found that peptide B1 showed specific cytotoxicity to tumor cells. Moreover, a helix-wheel plot predicted that the Ser14 in this peptide is located at the interface of the hydrophobic and hydrophilic faces of B1. Subsequently, we wondered whether replacing Ser14 would alter the activity of B1, and so a series of B1 analogs were synthesized where the Ser14 was replaced by amino acids with distinct physicochemical properties. Amongst them, peptides where Ser14 was substituted by a nonpolar and basic amino acid had improved anti-cancer activity. Further investigations revealed that B1 and its analogs were capable of penetrating into cytoplasm and triggering cytochrome C release from mitochondria, which ultimately resulted in apoptosis. Meanwhile, B1 and its analogs inhibited the migration of cancer cells. The peptides also acted against drug-resistant cells and had drug resistance-reversing effects. In conclusion, these peptides might be promising candidates for oncotherapy.
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Baowei
authors.initials: B
authors.lastname: Yang
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
authors.forename: Xuekun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China. Electronic address: ydhuangwenlong@126.com.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
authors.affiliation: Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China. Electronic address: qianhai24@163.com.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides
keywords: Anti-cancer; Drug resistance-reversing effects; Membrane-disruption; Peptides