Design and Investigation of Novel Antimicrobial Peptides with Dual Active Sequences

doi:10.7503/cjcu20120929

Abstract

Abstract:

Short antimicrobial peptides Combi-1 and Combi-2 have been selected as bioactive sequences for new antimicrobial peptide design. Linear and cyclic peptides with two bioactive sequences were designed, synthesized, investigated and compared to short peptides with single bioactive sequence. The results show that the antibacterial activity of linear and cyclic peptides is higher than that of short peptides. The binding energy between peptides and an important component of bacterial membrane phosphatidylglycerol(DMPG) was calculated by computer simulation. The results indicate that the binding energy between peptides and DMPG shows a high correlation to the antibacterial activity of peptides. The binding energy of linear or cyclic peptides with DMPG is also higher than that of short peptides. Linear and cyclic peptides with two bioactive sequences provide more positively charged amino acids, which bind to negatively charged phospholipid, leading to higher binding energy and stronger antibacterial activity. The computer simulation method provides theoretical evidence for antibacterial activity of antimicrobial peptides to some extent. The linear peptides and one short peptide Combi-1 which are low production cost show high antibacterial activity, low cytotoxicity and hemolytic activity, indicating a research and application potential. The mechanism of some designed peptides interacting with biomembrane was briefly investigated via mimic membrane. Other than forming pores on the cytoplasmic membrane of normal mammalian cells, these peptides do not form pores on bacterial membrane, but induce membrane aggregation, which indicate that membrane is not the main target for these peptides to kill the bacteria.

Key words: Antimicrobial peptide, Antibacterial activity, Peptide-phospholipid interaction, Computer simulation

CLC Number:

O629
R966

TrendMD:

YU Lan-Lan, MAO Ye-Xuan, BAI Xi-Xi, RAN Yu, LI Ai-Rong, ZHU Yan-Yan, YU Fei, QU Ling-Bo. Design and Investigation of Novel Antimicrobial Peptides with Dual Active Sequences[J]. Chem. J. Chinese Universities, 2013, 34(5): 1166.

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Design and Investigation of Novel Antimicrobial Peptides with Dual Active Sequences

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