title: Cyclization of the antimicrobial peptide gomesin with native chemical ligation: influences on stability and bioactivity.
abstract: Gomesin is an 18-residue peptide originally isolated from the hemocytes of the Brazilian spider Acanthoscurria gomesiana. A broad spectrum of bioactivities have been attributed to gomesin, including in vivo and in vitro cytotoxicity against tumour cells, antimicrobial, antifungal, anti-Leishmania and antimalarial effects. Given the potential therapeutic applications of gomesin, it was of interest to determine if an engineered version with a cyclic backbone has improved stability and bioactivity. Cyclization has been shown to confer enhanced stability and activity to a range of bioactive peptides and, in the case of a cone snail venom peptide, confer oral activity in a pain model. The current study demonstrates that cyclization improves the in vitro stability of gomesin over a 24 hour time period and enhances cytotoxicity against a cancer cell line without being toxic to a noncancerous cell line. In addition, antimalarial activity is enhanced upon cyclization. These findings provide additional insight into the influences of backbone cyclization on the therapeutic potential of peptides.
authors: The University of Queensland, Institute for Molecular Bioscience, 306 Carmody Road, Brisbane 4072, Australia.
authors: Lai Yue
authors: LY
authors: Chan
authors: Veronica M
authors: VM
authors: Zhang
authors: Yen-hua
authors: YH
authors: Huang
authors: Norman C
authors: NC
authors: Waters
authors: Paramjit S
authors: PS
authors: Bansal
authors: David J
authors: DJ
authors: Craik
authors: Norelle L
authors: NL
authors: Daly
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003500:Cyclization; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D055550:Protein Stability; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D013112:Spiders / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D000962:Antimalarials; D023181:Antimicrobial Cationic Peptides; C415987:gomesin