Chemistry Commons^™

Modified Synthesis Of The Peptidomimetic Natriuretic Peptide Receptor-C Antagonist M372049, Jacob Porter, Sergey V. Lindeman, Chris Dockendorff

Chemistry Faculty Research and Publications

The Natriuretic Peptide Receptors (NPRs) regulate vascular sodium levels and have been of significant interest for the potential treatment of hypertension and related cardiovascular complications. The peptidomimetic antagonist M372049 is a valuable probe for the study of NPR-C signaling, unfortunately it is presently not commercially available. Described is a detailed protocol for its synthesis that does not require specialized apparatus and builds upon a prior patent from Veale and colleagues. Key steps include a base-mediated lactam formation and a solid-supported peptide synthetic sequence. An X-ray crystal structure of a key lactam intermediate was obtained to confirm the structure and relative …