Synthesis and antibacterial studies of teixobactin analogues with non-isostere substitution of enduracididine

Kang Jin, Kathy Hiu Laam Po, Wang Yeuk Kong, Chung Hei Lo, Chun Wah Lo, Ho Yin Lam, Amaya Sirinimal, Jonathan Avraham Reuven, Sheng Chen, Xuechen Li

Research output: Journal article publicationJournal articleAcademic researchpeer-review

23 Citations (Scopus)

Abstract

Teixobactin is a structurally and mechanistically novel antimicrobial peptide with potent activities against Gram-positive pathogens. It contains L-allo-enduracididine (End) residue which is not readily accessible. In this report, we have used convergent Ser Ligation as the key step to prepare a series of teixobactin analogues with End being substituted with its non-isostere moieties. Among these analogues, compounds T16, T27 and T29 exhibited the best antimicrobial activities against different Gram-positive bacteria with MICs ranging from 0.25 to 1.0 µM. Structure-activity relationship is also established for further development of more promising teixobactin analogues.

Original languageEnglish
Pages (from-to)1062-1068
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume26
Issue number5
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • SAR study
  • Ser ligation
  • Teixobactin analogues

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this