C-terminal modification of a de novo designed antimicrobial peptide via capping of macrolactam rings

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

3 Scopus Citations
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Author(s)

  • Ping Zeng
  • Qipeng Cheng
  • Lanhua Yi
  • Sharon Shui Yee Leung
  • Kin-Fai Chan
  • Kwok-Yin Wong

Detail(s)

Original languageEnglish
Article number106251
Journal / PublicationBioorganic Chemistry
Volume130
Online published5 Nov 2022
Publication statusPublished - Jan 2023

Abstract

In this work, by capping a macrolactam ring at the C-terminus of a de novo-designed peptide, namely zp80, we have constructed a small peptide library via the solid phase peptide synthesis for screening. Eight peptides bearing different aspartic acid-rich macrolactam rings but the same linear (IIRR)4 unit exhibited improved antibacterial activities, hemolytic activity, and selectivity index. Mechanistic studies revealed that they could destroy the integrity of bacterial envelope, leading to cytoplasm leakage and rapid dissipation of membrane potential. One of these peptides, zp90 with a macrolactam ring of (KaDGD), demonstrated preferential interaction with calcium ions at a stoichiometric ratio of 1:1, promoting the affinity of designed peptides to bacterial membrane. Overall, this work provides a feasible strategy for medicinal chemists to further develop potent, selective, and multifunctional de novo-designed antimicrobial peptides.

Research Area(s)

  • Antimicrobial peptide, Calcium ion-binding affinity, Macrolactam ring, Membrane potential, Selectivity index

Citation Format(s)

C-terminal modification of a de novo designed antimicrobial peptide via capping of macrolactam rings. / Zeng, Ping; Cheng, Qipeng; Yi, Lanhua et al.
In: Bioorganic Chemistry, Vol. 130, 106251, 01.2023.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review