Development of triple-helical antimicrobial peptides

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860080
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Waseda University
• Principal Investigator: Masuda Ryo 早稲田大学, 理工学術院, その他 (90632159)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: コラーゲン / 抗菌ペプチド / 多剤耐性菌 / スクリーニング

Outline of Final Research Achievements

Antimicrobial peptides (AMPs) are promising alternatives for treating infections because of their broad antimicrobial spectra and their high selective toxicity against bacteria. However, the instability of peptides in bodily fluids is one of the major drawbacks that limit their in vivo use. Previously, we found peptides forming collagen-like triple-helical structures were stable in bodily fluid, because their rigid structures contributed to resistance against proteolytic enzymes.
Herein, we constructed a combinatorial library composed of triple-helical peptides. Screening of the peptide pools and the following structure-activity relationship study, we developed more potent peptide RR4. RR4 exhibited antimicrobial activity against both Gram-negative and Gram-positive bacteria, including multidrug resistant strains. Further study revealed RR4 exhibited antimicrobial activity by interaction with intercellular molecules such as DNA/RNA that inhibited cell division.

Free Research Field

ペプチド創薬