Synthesis and structure-activity relationship of teixobactin analogues via convergent Ser ligation

Kang Jin; Kathy Hiu Laam Po; Shengxi Wang; Jonathan Avraham Reuven; Chi Nga Wai; Ho Ting Lau; Ting Ho Chan; Sheng Chen; Xuechen Li

doi:10.1016/j.bmc.2017.04.039

Synthesis and structure-activity relationship of teixobactin analogues via convergent Ser ligation

Bioorg Med Chem. 2017 Sep 15;25(18):4990-4995. doi: 10.1016/j.bmc.2017.04.039. Epub 2017 Apr 29.

Authors

Kang Jin¹, Kathy Hiu Laam Po², Shengxi Wang³, Jonathan Avraham Reuven¹, Chi Nga Wai¹, Ho Ting Lau¹, Ting Ho Chan¹, Sheng Chen⁴, Xuechen Li⁵

Affiliations

¹ Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Hong Kong Special Administrative Region.
² Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region.
³ Faculty of Science, University of Alberta, Edmonton, Alberta, Canada.
⁴ Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region. Electronic address: sheng.chen@polyu.edu.hk.
⁵ Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: xuechenl@hku.hk.

PMID: 28495382
DOI: 10.1016/j.bmc.2017.04.039

Abstract

Convergent Ser/Thr ligation has been used to prepare a series of teixobactin analogues (28 in total) to establish a structure-activity relationship of teixobactin. anti-bacterial evaluations of these synthetic analogues have revealed the critical amino acid residues and the sites tolerable of modifications. These studies will shed lights on the further development of teixobactin analogues with improved antibacterial activities.

Keywords: SAR study; Ser/Thr ligation; Teixobactin analogues.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Depsipeptides / chemical synthesis
Depsipeptides / chemistry*
Depsipeptides / pharmacology
Methicillin-Resistant Staphylococcus aureus / drug effects
Microbial Sensitivity Tests
Serine / chemistry*
Staphylococcus aureus / drug effects
Structure-Activity Relationship
Threonine / chemistry

Substances

Anti-Bacterial Agents
Depsipeptides
Threonine
Serine
teixobactin