Issue 19, 2007
From the journal:

Organic & Biomolecular Chemistry

Biaryl amino acid templates in place of d-Pro-l-Pro in cyclic ß-hairpin cationic antimicrobial peptidomimetics

Nityakalyani Srinivas,a   Kerstin Moehle,a   Khaled Abou-Hadeed,a   Daniel Obrechtb  and  John A. Robinson*a  

* Corresponding authors

a Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
E-mail: robinson@oci.uzh.ch
Fax: (+41) 1-635-6833

b Polyphor AG, Gewerbestrasse 14, 4123 Allschwil, Switzerland

Abstract

The turn-forming D-Pro-L-Pro template has been frequently used to promote regular ß-hairpin conformations in cyclic protein epitope mimetics. Here the use of three isomeric biaryl templates has been studied as alternatives to D-Pro-L-Pro in the preparation of ß-hairpin peptidomimetics. The o,o′- o,m′- and m,m′-isomers of carboxymethyl- and aminomethyl-substituted biaryl templates have been incorporated into novel macrocyclic mimics of the naturally occurring cationic antimicrobial peptide protegrin I. The presence of the o-carboxymethyl-o′-aminomethyl-biaryl template within the macrocyclic peptide resulted in the appearance of slowly interconverting atropisomers. Although none of the resulting mimetics adopted stable ß-hairpin structures in aqueous solution, they all nevertheless retained a significant antimicrobial activity against Gram positive and Gram negative bacteria. These mimetics provide interesting starting points for an optimization program in the search for potent and novel antimicrobial compounds.

Graphical abstract: Biaryl amino acid templates in place of d-Pro-l-Pro in cyclic ß-hairpin cationic antimicrobial peptidomimetics

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Article information

DOI
https://doi.org/10.1039/B706370A
Article type
Paper
Submitted
27 Apr 2007
Accepted
11 Jul 2007
First published
17 Aug 2007

Org. Biomol. Chem., 2007,5, 3100-3105

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Biaryl amino acid templates in place of D-Pro-L-Pro in cyclic ß-hairpin cationic antimicrobial peptidomimetics

N. Srinivas, K. Moehle, K. Abou-Hadeed, D. Obrecht and J. A. Robinson, Org. Biomol. Chem., 2007, 5, 3100 DOI: 10.1039/B706370A

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