An adamantyl amino acid containing gramicidin S analogue with broad spectrum antibacterial activity and reduced hemolytic activity

Kapoerchan, V.V.
Knijnenburg, A.D.
Niamat, M.
Spalburg, E.
Neeling, A.J. de
Nibbering, P.H.
Mars-Groenendijk, R.H.
Noort, D.
Otero, J.M.
Llamas-Saiz, A.L.
Raaij, M.J. van
Marel, G.A. van der
Overkleeft, H.S.
Overhand, M.

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Publication date

January 2010

DOI

10.1002/chem.201001686

ISSN

0947-6539

Citation count (estimate)

Abstract

The cyclic cationic antimicrobial peptide gramicidin S (GS) is an effective topical antibacterial agent that is toxic for human red blood cells (hemolysis). Herein, we present a series of amphiphilic derivatives of GS with either two or four positive charges and characteristics ranging between very polar and very hydrophobic. Screening of this series of peptide derivatives identified a compound that combines effective antibacterial activity with virtually no toxicity within the same concentration range. This peptide acts against both Gram-negative and Gram-positive bacteria, including several MRSA strains, and represents an interesting lead for the development of a broadly applicable antibiotic. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Wein...