Bisubstrate inhibitors for the enzyme catechol-O-methyltransferase (COMT): influence of inhibitor preorganisation and linker length between the two substrate moieties on binding affinity

文献情報

出版日 2002-11-26

DOI 10.1039/B208690P

インパクトファクター 3.876

著者

Christian Lerner, Birgit Masjost, Armin Ruf, Volker Gramlich, Roland Jakob-Roetne, Gerhard Zürcher, Edilio Borroni, François Diederich

原文を見る

要旨

Inhibition of the enzyme catechol-O-methyltransferase (COMT) is an important approach in the treatment of Parkinson's disease. A series of new potent bisubstrate inhibitors for COMT, resulting from X-ray structure-based design and featuring adenosine and catechol moieties have been synthesised. Biological results show a large dependence of binding affinity on inhibitor preorganisation and the length of the linker between nucleoside and catechol moieties. The most potent bisubstrate inhibitor for COMT has an IC50 value of 9 nM. It exhibits competitive kinetics for the SAM and mixed inhibition kinetics for the catechol binding site. Its bisubstrate binding mode was confirmed by X-ray structure analysis of the ternary complex formed by the inhibitor, COMT and a Mg2+ ion.

掲載誌

Organic & Biomolecular Chemistry

CiteScore: 3.4

自己引用率: 10.3%

年間論文数: 1041

Organic & Biomolecular Chemistry (OBC) publishes original and high impact research and reviews in organic chemistry. We welcome research that shows new or significantly improved protocols or methodologies in total synthesis, synthetic methodology or physical and theoretical organic chemistry as well as research that shows a significant advance in the organic chemistry or molecular design aspects of chemical biology, catalysis, supramolecular and macromolecular chemistry, theoretical chemistry, mechanism-oriented physical organic chemistry, medicinal chemistry or natural products. Articles published in the journal should report new work which makes a highly-significant impact in the field. Routine and incremental work is generally not suitable for publication in the journal. More details about key areas of our scope are below. In all cases authors should include in their article clear rationale for why their research has been carried out.

Bisubstrate inhibitors for the enzyme catechol-O-methyltransferase (COMT): influence of inhibitor preorganisation and linker length between the two substrate moieties on binding affinity

文献情報

おすすめジャーナル

関連文献

Combination of Pd/C and Amberlyst-15 in a single reactor for the acid/hydrogenating catalytic conversion of carbohydrates to 5-hydroxy-2,5-hexanedione

Back cover

Tunable thermomorphism and applications of ionic liquid analogues of Girard's reagents

High-yield production of levulinic acid from cellulose and its upgrading to γ-valerolactone

Cobalt catalysts: very efficient for hydrogenation of biomass-derived ethyl levulinate to gamma-valerolactone under mild conditions

Towards the rational biosynthesis of substituted phenazines and phenoxazinones by laccases

General and selective reductive amination of carbonyl compounds using a core–shell structured Co3O4/NGr@C catalyst

Gold supported on titania for specific monohydrogenation of dinitroaromatics in the liquid phase

Electrocatalytic oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid on supported Au and Pd bimetallic nanoparticles

Enzymatic synthesis of ionic responsive lignin nanofibres through surface poly(N-isopropylacrylamide) immobilization

こちらもおすすめ

6-苄基-6,7-二氢-5H-吡咯并3,4-b吡啶とは何ですか？

半硫酸奎宁单水水合物はどのように保存すればよいですか？

D-核糖-5-リン酸二ナトリウムとは何ですか？

異丙基肼はどの業界で使用されていますか？

3-乙酰基-4-羟基喹啉-2(1H)-酮はどのように合成されますか？

Bobcat339はどのように保存すればよいですか？

5-溴-4-甲基-1H-吲唑とは何ですか？

3-(4メトキシフェニル)オキテナン-3カーボイル酸の代替品はありますか？

3-イリドオキシピロロ[2,3-b]ピリジン-5-カルボキシlic酸は安全ですか？

3-氟-4- iodobenolを取り扱う際の実験室安全事項は何ですか？

掲載誌

Organic & Biomolecular Chemistry

おすすめ化合物

trans-2-{[(Tert-butoxy)carbonyl]amino}cyclobutane-1-carboxylic acid

4-(1-Methyl-1H-pyrazol-4-yl)pyridine

Methyl 2-[5-(3-Phenoxyphenyl)-2H-tetrazol-2-yl]acetate

5-(Methoxymethoxy)-2-methylphenylboronic acid

5-Bromo-3-isopropyl-1H-pyrrolo[2,3-b]pyridine

おすすめサプライヤー