N-Methylated sst2 Selective Somatostatin Cyclic Peptide Analogue as a Potent Candidate for Treating Neurogenic Inflammation.

Abstract

A focused multiply N-methylated library of a cyclic hexapeptidic somatostatin analogue: MK678 cyclo(-MeAYwKVF-) was generated, which resulted in the unexpected observation of an efficacious tetra-N-methylated analogue, cyclo(-MeAYMewMeKVMeF-) with a potent inhibitory action on sensory neuropeptide release in vitro and on acute neurogenic inflammatory response in vivo. The analogue shows selectivity toward somatostatin receptor subtype 2 (sst2). Extensive 2D NMR spectroscopy and molecular dynamics simulation revealed the solution conformation of the analogue, which can be adopted as a lead for the further structure-activity relationship studies targeting neurogenic inflammation.

• Authors: Jayanta Chatterjee, Burkhardt Laufer, Johannes G Beck, Zsuzsanna Helyes, Erika Pintér, János Szolcsányi, Aniko Horvath, Jozsef Mandl, Jean C Reubi, György Kéri, Horst Kessler
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 2 Issue 7 Pg. 509-14 (Jul 14 2011) ISSN: 1948-5875 [Print] United States
• PMID: 24900340 (Publication Type: Journal Article)