The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F13%3A00396069" target="_blank" >RIV/61388963:_____/13:00396069 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.ejmech.2013.04.039" target="_blank" >http://dx.doi.org/10.1016/j.ejmech.2013.04.039</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2013.04.039" target="_blank" >10.1016/j.ejmech.2013.04.039</a>
Alternative languages
Result language
angličtina
Original language name
The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase
Original language description
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; weenhanced 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 pharmacolog
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CE - Biochemistry
OECD FORD branch
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Result continuities
Project
<a href="/en/project/GAP207%2F10%2F1277" target="_blank" >GAP207/10/1277: New inhibitors for human methyltransferases BHMT and BHMT-2 to study their physiological functions</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2013
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Medicinal Chemistry
ISSN
0223-5234
e-ISSN
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Volume of the periodical
65
Issue of the periodical within the volume
July
Country of publishing house
FR - FRANCE
Number of pages
20
Pages from-to
256-275
UT code for WoS article
000322850100026
EID of the result in the Scopus database
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