A fragment of the Escherichia coli ClpB heat-shock protein is a micromolar melanocortin 1 receptor agonist

Mark D. Ericson, Sathya M. Schnell, Katie T. Freeman, Carrie Haskell-Luevano

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The melanocortin system consists of five receptor subtypes (MC1-5R), endogenous agonists derived from the proopiomelanocortin gene transcript, and the antagonists agouti and agouti-related protein. The Escherichia coli heat shock protein ClpB has previously been described as an antigen mimetic to the endogenous melanocortin agonist α-MSH. Herein, we investigated if a fragment of the ClpB protein could directly signal through the melanocortin receptors. We synthesized a complementary fragment of the ClpB protein that partially aligned with α-MSH. Pharmacological assessment of this fragment resulted in no antagonist activity at the MC3R or the MC4R and no agonist activity at the MC4R. Partial receptor activation was observed for the MC3R and MC5R at 100 μM concentrations. This fragment was shown to be a full micromolar MC1R agonist and may serve as a template for future research into selective MC1R ligands.

Original languageEnglish (US)
Pages (from-to)5306-5308
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number22
DOIs
StatePublished - Nov 15 2015

Bibliographical note

Funding Information:
This work has been supported by NIH Grants R01DK097838 and R01DK091906 .

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