Journal article

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

Wenyi Li, Julien Tailhades, M Akhter Hossain, Neil M O'Brien-Simpson, Eric C Reynolds, Laszlo Otvos, Frances Separovic, John D Wade



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..

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Awarded by ARC Discovery Project

Awarded by NHMRC Project

Funding Acknowledgements

We gratefully acknowledge support of the studies undertaken in the authors' laboratory by an ARC Discovery Project grant (DP150103522) to JDW and MAH, and an NHMRC Project grants (APP1029878) to NMOBS and (APP1008106) to ECR and NMOBS. JDW is an NHMRC (Australia) Principal Research Fellow. Research at the FNI was also supported by the Victorian Government's Operational Infrastructure Support Program. WL acknowledges the University of Melbourne for a MIRS PhD award. Thank you to Shu Jie Lam for assistance with NMR spectroscopy.