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

Uru Malik, Lai Yue Chan, Minying Cai, Victor J Hruby, Quentin Kaas, Norelle L. Daly, David J. Craik

Research output: Contribution to journalArticlepeer-review

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 μM. 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.

Original languageEnglish (US)
JournalPeptide Science
DOIs
StateAccepted/In press - 2020

Keywords

  • antagonist
  • backbone cyclization
  • binding
  • frog-skin peptides
  • melanocortin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Development of novel frog-skin peptide scaffolds with selectivity towards melanocortin receptor subtypes'. Together they form a unique fingerprint.

Cite this