Solomon Gisemba

Solomon Gisemba

Postdoctoral Research Associate
University of Florida
Gainesville, FL
USA
 sgisemba@ufl.edu

Abstract

Synthesis of Bicyclic Analogs of the Kappa Opioid Receptor Antagonist Arodyn

The acetylated dynorphin A analog arodyn (Ac[Phe1,2,3,Arg4,D-Ala8]Dyn A(1-11)-NH2) exhibits potent and selective kappa opioid receptor antagonism. While cyclization can impart metabolic stability, increase binding affinity, and/or improve permeability, bicyclization imparts additional conformational constraint which can further enhance metabolic stability.

There have been increasing reports and interest in bicyclic peptides, but to the best of our knowledge there are currently no reports of bicyclic opioid peptides, possibly due to the short length of the most extensively studied opioid peptides.

Based on structure-activity relationships of monocyclic arodyn analogs, we designed two bicyclic arodyn analogs using ring closing metathesis, RCM, and lactam chemistries. Here we report the synthesis and opioid receptor binding affinities of the bicyclic arodyn analogs. Research supported by NIDA grant R01 DA018832.

Lecture Images

Solomon Gisemba presenting at APS2019 Solomon Gisemba presenting at APS2019 Solomon Gisemba presenting at APS2019