Journal article

The Effect of Selective D- or N-alpha-Methyl Arginine Substitution on the Activity of the Proline-Rich Antimicrobial Peptide, Chex1-Arg20

Wenyi Li, Zhe Sun, Neil M O'Brien-Simpson, Laszlo Otvos, Eric C Reynolds, Mohammed A Hossain, Frances Separovic, John D Walde



In vivo pharmacokinetics studies have shown that the proline-rich antimicrobial peptide, A3-APO, which is a discontinuous dimer of the peptide, Chex1-Arg20, undergoes degradation to small fragments at positions Pro6-Arg7 and Val19-Arg20. With the aim of minimizing or abolishing this degradation, a series of Chex1-Arg20 analogs were prepared via Fmoc/tBu solid phase peptide synthesis with D-arginine or, in some cases, peptide backbone Nα-methylated arginine, substitution at these sites. All the peptides were tested for antibacterial activity against the Gram-negative bacterium Klebsiella pneumoniae. The resulting activity of position-7 substitution of Chex1-Arg20 analogs showed that arginine-..

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Awarded by ARC Discovery Project

Awarded by NHMRC Project

Funding Acknowledgements

We gratefully acknowledge support of studies undertaken in the authors' laboratory by ARC Discovery Project grants (DP150103522) to JW and MH, and NHMRC Project grants (APP1029878) to NMOBS and (APP1008106) to ER and NMOBS. JW is an NEIMRC (Australia) Principal Research Fellow. WL is the recipient of an MIRS PhD award and Dr Albert Shimmins Postgraduate Writing-Up award (University of Melbourne). Research at the FINMH was also supported by the Victorian Government's Operational Infrastructure Support Program.