Journal of Medicinal Chemistry p. 152 - 158 (1975)
Update date:2022-09-26
Topics:
Borchardt
Thakker
Several N acyl 4 hydroxy 3,5 dimethoxy phenylalkylamines were synthesized and evaluated for ability to inactivate catechol O methyltransferase (COMT). 4 Hydroxy N iodoacetyl 3,5 dimethoxy phenylethylamine was found to rapidly and irreversibly inactivate this enzyme. The corresponding n concentrations bromoacetyl derivative also produced inactivation of COMT but at a slower rate than the N iodoacetyl derivative. The N acetyl and N fumaryl derivatives were completely inactive. Inactivation of COMT by these reagents appears to proceed by a unimolecular reaction within a dissociable complex rather than by a nonspecific bimolecular reaction. The proximity of the amino acid residue being modified relative to the site which binds the aromatic portion of these inhibitors was determined using N iodoactylphenylalkylamines of varying chain length. The number of methylene carbons separating the aromatic ring and the iodoacetamide moiety in these inhibitors did not greatly influence the binding to COMT nor did it affect how rapidly the enzyme was inactivated. From these observations it is concluded that the amino acid moiety being modified by this class of affinity labeling reagents must be relatively close to or part of the site which binds the aromatic region of these inhibitors.
View MoreContact:+86-371-86058576
Address:NO.32, Jingsan Road, Zhengzhou, China
Contact:13120882795;+86-21-34621078;+86-021-31122318
Address:Suite 2,No.2715 Longwu Road
Contact:+86-20-62802632;62802633
Address:Room 330 GIGCAS Building,No.511 Kehua Street,Tianhe District
Contact:17316303296
Address:240 Amboy Ave
QINGDAO HONG JIN CHEMICAL CO.,LTD.
website:http://www.hongjinchem.com
Contact:+86-532-83657313
Address:2ND Building, 8 Shangqing Road, Qingdao, Shandong Province, China.
Doi:10.1002/cssc.201100361
(2011)Doi:10.1002/chem.201903464
(2019)Doi:10.1039/c7cc07111f
(2017)Doi:10.1016/j.apcata.2015.11.031
(2016)Doi:10.1007/BF00474318
()Doi:10.1016/S0960-894X(02)00951-4
(2003)