1. Academic Validation
  2. Antimicrobial Peptides with High Proteolytic Resistance for Combating Gram-Negative Bacteria

Antimicrobial Peptides with High Proteolytic Resistance for Combating Gram-Negative Bacteria

  • J Med Chem. 2019 Mar 14;62(5):2286-2304. doi: 10.1021/acs.jmedchem.8b01348.
Jiajun Wang 1 Jing Song 1 Zhanyi Yang 1 Shiqi He 1 Yi Yang 1 Xingjun Feng 1 Xiujing Dou 1 Anshan Shan 1
Affiliations

Affiliation

  • 1 Institute of Animal Nutrition , Northeast Agricultural University , Harbin 150030 , P. R. China.
Abstract

Poor proteolytic resistance is an urgent problem to be solved in the clinical application of antimicrobial Peptides (AMPs), yet common solutions, such as complicated chemical modifications and utilization of d-amino acids, greatly increase the difficulty and cost of producing AMPs. In this work, a set of novel Peptides was synthesized based on an antitrypsin/antichymotrypsin hydrolytic peptide structure unit (XYPX) n (X represents I, L, and V; Y represents R and K), which was designed using a systematic natural amino acid arrangement. Of these Peptides, 16 with seven repeat units had the highest average selectivity index (GMSI = 99.07) for all of the Gram-negative bacteria tested and remained highly effective in combating Escherichia coli Infection in vivo. Importantly, 16 also had dramatic resistance to a high concentration of trypsin/chymotrypsin hydrolysis and exerted bactericidal activity through a membrane-disruptive mechanism. Overall, these findings provide new approaches for the development of antiprotease hydrolytic Peptides that target Gram-negative bacteria.

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