title: 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.affiliation: Institute for Advanced Study and Center for Integrated Protein Science at the Department Chemie, Technische Universität München , Lichtenbergstrasse 4, Garching 85747, Germany.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chatterjee
authors.affiliation: Institute for Advanced Study and Center for Integrated Protein Science at the Department Chemie, Technische Universität München , Lichtenbergstrasse 4, Garching 85747, Germany.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Laufer
authors.affiliation: Institute for Advanced Study and Center for Integrated Protein Science at the Department Chemie, Technische Universität München , Lichtenbergstrasse 4, Garching 85747, Germany.
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Beck
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs , H-7624, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs , H-7624, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Pécs , H-7624, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Szolcsányi
authors.affiliation: Pathobiochemistry Research Group of Hungarian Academy of Sciences in Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University , Budapest, H-1094, Hungary.
authors.forename: Aniko
authors.initials: A
authors.lastname: Horvath
authors.affiliation: Pathobiochemistry Research Group of Hungarian Academy of Sciences in Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University , Budapest, H-1094, Hungary.
authors.forename: Jozsef
authors.initials: J
authors.lastname: Mandl
authors.affiliation: Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Bern , Bern, CH-3010 Switzerland.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Reubi
authors.affiliation: Pathobiochemistry Research Group of Hungarian Academy of Sciences in Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University , Budapest, H-1094, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Kéri
authors.affiliation: Institute for Advanced Study and Center for Integrated Protein Science at the Department Chemie, Technische Universität München , Lichtenbergstrasse 4, Garching 85747, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
keywords: N-methylated peptide; Somatostatin; cyclic peptide; multiple N-methylation; neurogenic inflammation; sst