Thiol-ene Enabled Chemical Synthesis of Truncated S-Lipidated Teixobactin Analogs

Victor V Yim; Alan J Cameron; Iman Kavianinia; Paul W R Harris; Margaret A Brimble

doi:10.3389/fchem.2020.00568

Thiol-ene Enabled Chemical Synthesis of Truncated S-Lipidated Teixobactin Analogs

Front Chem. 2020 Aug 4:8:568. doi: 10.3389/fchem.2020.00568. eCollection 2020.

Authors

Victor V Yim^{1

2}, Alan J Cameron^{1

2

3}, Iman Kavianinia^{1

2

3}, Paul W R Harris^{1

2

3}, Margaret A Brimble^{1

2

3}

Affiliations

¹ School of Biological Sciences, University of Auckland, Auckland, New Zealand.
² School of Chemical Sciences, University of Auckland, Auckland, New Zealand.
³ Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.

Abstract

Herein is described the introduction of lipid moieties onto a simplified teixobactin pharmacophore using a modified Cysteine Lipidation on a Peptide or Amino acid (CLipPA) technique, whereby cysteine was substituted for 3-mercaptopropionic acid (3-MPA). A truncated teixobactin analog was prepared with the requisite thiol handle, thus enabling an array of vinyl esters to be conveniently conjugated onto the simplified teixobactin pharmacophore to yield S-lipidated cyclic lipopeptides.

Keywords: AMP; antimicrobial peptide; lipidation; lipopeptide; modified CLipPA; teixobactin; thiol-ene.