Total synthesis and a systematic structure-activity relationship study of WAP-8294A2

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Delin Chen
  • Liwen Tian
  • Kathy Hiu Laam Po
  • Sheng Chen
  • Xuechen Li

Detail(s)

Original languageEnglish
Article number115677
Journal / PublicationBioorganic and Medicinal Chemistry
Volume28
Issue number18
Online published30 Jul 2020
Publication statusPublished - 15 Sep 2020

Abstract

WAP-8294A2 is a cyclic peptide antibiotic with novel structure and excellent activity against Gram-positive pathogens. Herein, we report the total synthesis of complex macrocyclic peptide WAP-8294A2 (W1), ent-analogue W2, deoxy analogue W3 and de-methyl analogue W4 using a solid-phase synthetic route followed by a final stage solution-phase cyclization reaction. Exploitation of this process allowed the synthesis of eleven alanine-scanning analogues and eight lysine-scanning analogues. The antimicrobial activity of these analogues was evaluated in vitro against Gram-positive bacteria. Based on the MIC results, a primary systematic structure-activity relationship has been established.

Research Area(s)

  • Alanine scan, Lysine scan, Total synthesis, WAP-8294A2

Bibliographic Note

Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation Format(s)

Total synthesis and a systematic structure-activity relationship study of WAP-8294A2. / Chen, Delin; Tian, Liwen; Po, Kathy Hiu Laam; Chen, Sheng; Li, Xuechen.

In: Bioorganic and Medicinal Chemistry, Vol. 28, No. 18, 115677, 15.09.2020.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal