Double-Headed Sulfur-Linked Amino Acids As First Inhibitors for Betaine-Homocysteine S-Methyltransferase 2

0379825 - ÚOCHB 2013 RIV US eng J - Journal Article
Mládková, Jana - Vaněk, Václav - Buděšínský, Miloš - Elbert, Tomáš - Demianova, Zuzana - Garrow, T. A. - Jiráček, Jiří
Double-Headed Sulfur-Linked Amino Acids As First Inhibitors for Betaine-Homocysteine S-Methyltransferase 2.
Journal of Medicinal Chemistry. Roč. 55, č. 15 (2012), s. 6822-6831. ISSN 0022-2623. E-ISSN 1520-4804
R&D Projects: GA ČR GA203/09/1919; GA ČR(CZ) GAP207/10/1277
Institutional support: RVO:61388963
Keywords : betaine * homocysteine * methionine * BHMT * inhibitor
Subject RIV: CE - Biochemistry
Impact factor: 5.614, year: 2012

BHMT-2 methyltransferase catalyzes the transfer of a methyl group from S-methylmethionine to L-homocysteine, yielding two molecules of L-methionine. In this study, we have prepared the first series of BHMT-2 inhibitors to be described, and we have tested them with human recombinant BHMT-2 that has been stabilized by copurification with human recombinant BHMT. Among the compounds synthesized, (2S,8RS,11RS)-5-thia-2,11-diamino-8-methyldodecanedioic acid was the most potent (Ki app about 77 nM) and selective inhibitor of BHMT-2. This compound may be useful in future in vivo studies to probe the physiological significance of BHMT-2 in sulfur amino acid metabolism.
Permanent Link: http://hdl.handle.net/11104/0210696