Synthetic Peptides as cGMP-Independent Activators of cGMP-Dependent Protein Kinase I α

In this study, a set of synthetic peptides (S-tides), derived from this helix, was found to bind to and activate PKG Iα in a cyclic guanosine monophosphate (cGMP)-independent manner. The most potent S-tide derivative (S1.5) increased the open probability of the potassium channel KCa1.1 to levels equivalent to saturating cGMP. Introduction of S1.5 to smooth muscle cells in isolated, endothelium-denuded cerebral arteries through a modified reversible permeabilization procedure inhibited myogenic constriction. In contrast, in endothelium-intact vessels S1.5 had no effect on myogenic tone. This suggests that PKG Iα activation by S1.5 in vascular smooth muscle would be sufficient to inhibit augmented arterial contractility that frequently occurs following endothelial damage associated with cardiovascular disease. PMID:26687482 | PMC:PMC4703045 | DOI:10.1016/j.chembiol.2015.11.005

Source: Chemistry and Biology - December 22, 2015 Category: Chemistry Authors: Thomas M Moon Nathan R Tykocki Jessica L Sheehe Brent W Osborne Werner Tegge Joseph E Brayden Wolfgang R Dostmann Source Type: research