4.3 Article

A Novel Trp-rich Model Antimicrobial Peptoid with Increased Protease Stability

Journal

BULLETIN OF THE KOREAN CHEMICAL SOCIETY
Volume 31, Issue 9, Pages 2509-2513

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.5012/bkcs.2010.31.9.2509

Keywords

Peptoid; Protease stability; Trp-rich model antimicrobial peptide

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In order to increase protease stability of a novel Trp-rich model antimicrobial peptide, K6L2W3(KLWKKWKKWLK-NH2) and investigate the effect of L-amino acid to peptoid residue conversion on biological functions, we synthesized its antimicrobial peptoid, k(6)l(2)w(3). Peptoid k(6)l(2)w(3) had similar bacterial selectivity compared to peptide K6L2W3. The bactericidal rate of k(6)l(2)w(3) was somewhat slower than that of K6L2W3. Peptoid k(6)l(2)w(3) exhibited very little dye leakage from bacterial outer-membrane mimicking PE/PG liposomes, as observed in K6L2W3, indicating that the major target site of K6L2W3 and k(6)l(2)w(3) may be not the cell membrane but the cytoplasm of bacteria. Trypsin treatment of K6L2W3 completely abolished antimicrobial activities against Escherichia coli and Staphylococcus aureus. In contrast, the antimicrobial activity of k(6)l(2)w(3) was completely preserved after trypsin treatment. Taken together, our results suggested that antimicrobial peptoid k(6)l(2)w(3) can potentially serves as a promising therapeutic agent for the treatment of microbial infection.

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