Development of novel frog-skin peptide scaffolds with selectivity towards melanocortin receptor subtypes

Malik, Uru, Chan, Lai Yue, Cai, Minying, Hruby, Victor J., Kaas, Quentin, Daly, Norelle L., and Craik, David J. (2021) Development of novel frog-skin peptide scaffolds with selectivity towards melanocortin receptor subtypes. Peptide Science, 113 (4). e24209.

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Abstract

Melanocortin receptors are pharmaceutically important receptors that are involved in complex physiological functions. They have been associated with various diseases including obesity, erectile dysfunction, acne, and skin cancer. It has been challenging to transform nonselective endogenous agonist and antagonist ligands into selective and potent ligands. In this study, we investigated naturally occurring peptides derived from frog skin secretions for selectivity and activity toward melanocortin receptors. Three peptides (ORB, ORB2K and ranacyclin-T) were found to have selectivity towards the melanocortin receptor 5 (MC5R). ORB and ORB2K had partial binding affinity at nanomolar concentrations, whereas ranacyclin-T had 57% binding efficiency at 1.6 mu M. Backbone cyclization of ORB and ORB2K altered the binding efficiency to melanocortin receptors. Our results suggest that these frog-skin peptides could be modified for developing melanocortin-specific ligands and potentially future therapeutics.

Item ID: 65091
Item Type: Article (Research - C1)
ISSN: 1097-0282
Keywords: antagonist, backbone cyclization, binding, frog&#8208, skin peptides, melanocortin
Copyright Information: © 2020 Wiley Periodicals LLC
Funders: Australian Research Council (ARC), National Health and Medical Research Council (NHMRC)
Projects and Grants: ARC Grant/Award Number: FL150100146, ARC Grant/Award Number: FT1100100226, NHMRC Grant/Award Number: APP1028509
Date Deposited: 18 Nov 2020 07:41
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Last 12 Months: 1
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