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Plant Antimicrobial Peptides Snakin‐1 and Snakin‐2: Chemical Synthesis and Insights into the Disulfide Connectivity
Author(s) -
Harris Paul W. R.,
Yang SungHyun,
Molina Antonio,
López Gemma,
Middleditch Martin,
Brimble Margaret A.
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201303207
Subject(s) - native chemical ligation , chemistry , cysteine , oxidative folding , cystine , trypsin , antimicrobial , peptide , combinatorial chemistry , disulfide bond , antifungal , antimicrobial peptides , mass spectrometry , cyclic peptide , biochemistry , thiazolidine , solid phase synthesis , organic chemistry , chromatography , biology , enzyme , microbiology and biotechnology
Antimicrobial peptides and proteins represent an important class of plant defensive compounds against pathogens and provide a rich source of lead compounds in the field of drug discovery. We describe the effective preparation of the cysteine‐rich snakin‐1 and ‐2 antimicrobial peptides by using a combination of solid‐phase synthesis and native chemical ligation. A subsequent cysteine/cystine mediated oxidative folding to form the six internal disulfide bonds concurrently gave the folded proteins in 40–50 % yield. By comparative evaluation of mass spectrometry, HPLC, biological data and trypsin digest mapping of folded synthetic snakin‐2 compared to natural snakin‐2, we demonstrated that synthetic snakin‐2 possesses full antifungal activity and displayed similar chromatographic behaviour to natural snakin‐2. Trypsin digest analysis allowed tentative assignment of three of the purported six disulfide bonds.