Journal article
Enhancing proline-rich antimicrobial peptide action by homodimerization: Influence of bifunctional linker
W Li, F Lin, A Hung, A Barlow, MA Sani, R Paolini, W Singleton, J Holden, MA Hossain, F Separovic, NM O'Brien-Simpson, JD Wade
Chemical Science | Published : 2022
DOI: 10.1039/d1sc05662j
Abstract
Antimicrobial peptides (AMPs) are host defense peptides, and unlike conventional antibiotics, they possess potent broad spectrum activities and, induce little or no antimicrobial resistance. They are attractive lead molecules for rational development to improve their therapeutic index. Our current studies examined dimerization of the de novo designed proline-rich AMP (PrAMP), Chex1-Arg20 hydrazide, via C-terminal thiol addition to a series of bifunctional benzene or phenyl tethers to determine the effect of orientation of the peptides and linker length on antimicrobial activity. Antibacterial assays confirmed that dimerization per se significantly enhances Chex1-Arg20 hydrazide action. Great..
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Awarded by Australian Government
Funding Acknowledgements
We thank Professor Jian Li, Monash Biomedicine Discovery Institute, Monash University, Australia, for critical advice during the course of this work. We acknowledge the Melbourne Cytometry Platform (Melbourne Dental School, The University of Melbourne) for the provision of flow cytometry services. The HIM work was performed in part at the Materials Characterization and Fabrication Platform (MCFP) at the University of Melbourne and the Victorian Node of the Australian National Fabrication Facility (ANFF). Computational resources were provided by the National Computational Infrastructure (NCI), which is supported by the Australian Government, and the Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia. This work was supported by grants to W. L. (University of Melbourne Early Career Researcher Grant, Weary Dunlop Foundation Grant and Australian Dental Research Foundation Grant 2545-2020), to J. D. W. (NHMRC Project grant APP1158841, NHMRC Principal Research Fellowship APP1117483); to N. M. O-S (NHMRC Project grants APP1142472, APP1158841, APP1185426, ARC funding DP210102781, DP160101312, LE200100163) and Australian Dental Research Funding in antimicrobial materials. W. L. acknowledges NHMRC funding (APP1185426) to support his salary. Studies at the FINMH were supported by the Victorian Government's Operational Infrastructure Support Program.