Palucki B L, Feighner S D, Pong S, McKee K K, Hreniuk D L, Tan C, Howard A D, Van der Ploeg L H, Patchett A A, Nargund R P
Department of Medicinal Chemistry, Merck Research Laboratories, 07065, Rahway, NJ, USA.
Bioorg Med Chem Lett. 2001 Jul 23;11(14):1955-7. doi: 10.1016/s0960-894x(01)00324-9.
A series of small molecules derived from MK-0677, a potent synthetic GHS, mimicking the N-terminal Gly-Ser-O-(n-octanoyl)-L-Ser-Phe segment of ghrelin was synthesized and tested in a binding and in a functional assay measuring intracellular calcium elevation in HEK-293 cells expressing hGHSR1a. Replacement of Phe in this tetrapeptide with a spiro(indoline-3,4'-piperidine) group, Gly-Ser with 2-aminoisobutyric acid, and O-(n-octanoyl)-L-Ser with O-benzyl-D-Ser provided synthetic GHS agonists with similar functional potency as ghrelin.
合成了一系列源自强效合成生长激素促分泌素（GHS）MK-0677的小分子，这些小分子模拟了胃饥饿素的N端甘氨酸-丝氨酸-O-（正辛酰基）-L-丝氨酸-苯丙氨酸片段，并在结合实验以及测量表达人GHSR1a的HEK-293细胞内钙升高的功能实验中进行了测试。用螺环（吲哚啉-3,4'-哌啶）基团取代该四肽中的苯丙氨酸，用2-氨基异丁酸取代甘氨酸-丝氨酸，并用O-苄基-D-丝氨酸取代O-（正辛酰基）-L-丝氨酸，得到了与胃饥饿素功能效力相似的合成GHS激动剂。
