Chatterjee Jayanta, Laufer Burkhardt, Beck Johannes G, Helyes Zsuzsanna, Pintér Erika, Szolcsányi János, Horvath Aniko, Mandl Jozsef, Reubi Jean C, Kéri György, Kessler Horst
Institute for Advanced Study and Center for Integrated Protein Science at the Department Chemie, Technische Universität München , Lichtenbergstrasse 4, Garching 85747, Germany.
Department of Pharmacology and Pharmacotherapy, University of Pécs , H-7624, Hungary.
ACS Med Chem Lett. 2011 Apr 4;2(7):509-14. doi: 10.1021/ml200032v. eCollection 2011 Jul 14.
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.
MK678环（-MeAYwKVF-），意外发现了一种有效的四甲基化类似物环（-MeAYMewMeKVMeF-），它在体外对感觉神经肽释放以及在体内对急性神经源性炎症反应具有强效抑制作用。该类似物对生长抑素受体亚型2（sst2）具有选择性。广泛的二维核磁共振光谱和分子动力学模拟揭示了该类似物的溶液构象，可将其用作针对神经源性炎症的进一步构效关系研究的先导物。
