Journal of Medicinal Chemistry p. 6864 - 6874 (2004)
Update date:2022-07-29
Topics:
Lavrador, Karine
Murphy, Brian
Saunders, John
Struthers, Scott
Wang, Xiaochuan
Williams, John
One subset of the G-protein coupled receptor (GPCR) super-family is that which is activated by a peptide carrying an obligatory positively charged residue (GPCR-PA+). This subclass is exemplified by receptors for melanocortins, GnRH, galanin, MCH, orexin, and some chemokine receptors variously involved in eating disorders, reproductive disorders, pain, narcolepsy, obesity, and inflammation. Using the methods described in this study, a region of chemical property space enriched in GPCR ligands was identified. This information was used to design and synthesize a "test" library of 2025 single, pure compounds to sample portions of this property space associated with GPCR-PA+ ligands. The library was evaluated by high-throughput screening against three different receptors, rMCH, hMC4, and hGnRH, and found to be highly enriched in active ligands (4.5-61-fold) compared to a control set of 2024 randomly selected compounds. In addition, the analysis suggested that about 7000 compounds will be necessary to complete the sampling of this GPCR-PA+ ligand-rich region and to better define its borders.
View MoreContact:0572-2722882
Address:1201,F3,xinghuibandao,
Suzhou Jingye Medicine & Chemical Co., Ltd
website:http://www.jingyechem.cn
Contact:+86-512-66658588
Address:No. 88, Sanlian Street, Jinfeng Road, Suzhou New District, Jiangsu Province, P. R. China
Chengdu ZY Biochemical Technology Co., LTD
Contact:0086-28-88680086
Address:170 Qingpu Road, Shouan Town, Pujiang County
Contact:+44 7958 511245
Address:PO Box 469, Manchester, UK
Contact:+86-025-52406782
Address:8 Taizishan Rd., Yanjiang Industrial Development Area, Nanjing, Jiangsu, China.
Doi:10.1002/cber.19961290506
(1996)Doi:10.1016/0040-4020(82)85111-9
(1982)Doi:10.1007/BF00956006
(1982)Doi:10.1039/c3cc45367g
(2013)Doi:10.1016/0040-4020(96)00467-X
(1996)Doi:10.1080/10426509708545677
(1997)