"CLipP"ing on lipids to generate antibacterial lipopeptides

Victor Yim; Iman Kavianinia; Melanie K Knottenbelt; Scott A Ferguson; Gregory M Cook; Simon Swift; Aparajita Chakraborty; Jane R Allison; Alan J Cameron; Paul W R Harris; Margaret A Brimble

doi:10.1039/d0sc01814g

"CLipP"ing on lipids to generate antibacterial lipopeptides

Chem Sci. 2020 May 20;11(22):5759-5765. doi: 10.1039/d0sc01814g.

Authors

Victor Yim^{1

2}, Iman Kavianinia^{1

3

2}, Melanie K Knottenbelt⁴, Scott A Ferguson⁴, Gregory M Cook⁴, Simon Swift⁵, Aparajita Chakraborty^{1

3}, Jane R Allison^{1

3}, Alan J Cameron^{1

3}, Paul W R Harris^{1

3

2}, Margaret A Brimble^{1

3

2}

Affiliations

¹ School of Biological Sciences, University of Auckland 3A Symonds Street Auckland 1010 New Zealand.
² School of Chemical Sciences, University of Auckland 23 Symonds Street Auckland 1010 New Zealand.
³ Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland 3A Symonds Street Auckland 1010 New Zealand.
⁴ Department of Microbiology and Immunology, School of Medical Sciences, University of Otago 720 Cumberland Street Dunedin 9054 New Zealand.
⁵ Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland 85 Park Road, Grafton Auckland 1023 New Zealand.

Abstract

We herein report the synthesis and biological and computational evaluation of 12 linear analogues of the cyclic lipopeptide battacin, enabled by Cysteine Lipidation on a Peptide or Amino Acid (CLipPA) technology. Several of the novel "CLipP"ed lipopeptides exhibited low micromolar MICs and MBCs against both Gram-negative and Gram-positive bacteria. The mechanism of action was then simulated with the MIC data using computational methods.