Počet záznamů: 1
The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase
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SYSNO ASEP 0396069 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase Tvůrce(i) Pícha, Jan (UOCHB-X) RID, ORCID
Vaněk, Václav (UOCHB-X) RID, ORCID
Buděšínský, Miloš (UOCHB-X) RID, ORCID
Mládková, Jana (UOCHB-X)
Garrow, T. A. (US)
Jiráček, Jiří (UOCHB-X) RID, ORCIDCelkový počet autorů 6 Zdroj.dok. European Journal of Medicinal Chemistry. - : Elsevier - ISSN 0223-5234
Roč. 65, July (2013), s. 256-275Poč.str. 20 s. Jazyk dok. eng - angličtina Země vyd. FR - Francie Klíč. slova BHMT ; inhibitor ; homocysteine ; phosphonate ; phosphinate ; amino acid derivative ; bioisostere ; S-alkylated homocysteine Vědní obor RIV CE - Biochemie CEP GAP207/10/1277 GA ČR - Grantová agentura ČR Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000322850100026 EID SCOPUS 84878214075 DOI 10.1016/j.ejmech.2013.04.039 Anotace Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely define the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Rok sběru 2014
Počet záznamů: 1