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RESEARCH FRONT
Contents Vol 68(9)

C-Terminal Modifications Broaden Activity of the Proline-Rich Antimicrobial Peptide, Chex1-Arg20

Wenyi Li A B , Julien Tailhades B , M. Akhter Hossain A B , Neil M. O’Brien-Simpson C D , Eric C. Reynolds C D , Laszlo Otvos Jr E , Frances Separovic A C F and John D. Wade A B F
+ Author Affiliations
- Author Affiliations

A School of Chemistry, University of Melbourne, Melbourne, Vic. 3010, Australia.

B The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic. 3010, Australia.

C Bio21 Institute, University of Melbourne, Melbourne, Vic. 3010, Australia.

D Oral Health CRC, Melbourne Dental School, University of Melbourne, Melbourne, Vic. 3010, Australia.

E Department of Biology, Temple University, Philadelphia, PA 19122, USA.

F Corresponding authors. Email: fs@unimelb.edu.au; john.wade@florey.edu.au

Australian Journal of Chemistry 68(9) 1373-1378 https://doi.org/10.1071/CH15169
Submitted: 8 April 2015  Accepted: 21 May 2015   Published: 12 June 2015

Abstract

A series of N- and C-terminal modifications of the monomeric proline-rich antimicrobial peptide, Chex1-Arg20, was obtained via different chemical strategies using Fmoc/tBu solid-phase peptide synthesis in order to study their effects on a panel of Gram-negative bacteria. In particular, C-terminal modifications with hydrazide or alcohol functions extended their antibacterial activity from E. coli and K. pneumoniae to other Gram-negative species, A. baumannii and P. aeruginosa. Furthermore, these analogues did not show cytotoxicity towards mammalian cells. Hence, such modifications may aid in the development of more potent proline-rich antimicrobial peptides with a greater spectrum of activity against Gram-negative bacteria than the parent peptide.


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