Bisubstrate inhibitors for the enzyme catechol-O-methyltransferase (COMT): influence of inhibitor preorganisation and linker length between the two substrate moieties on binding affinity
文献信息
Christian Lerner, Birgit Masjost, Armin Ruf, Volker Gramlich, Roland Jakob-Roetne, Gerhard Zürcher, Edilio Borroni, François Diederich
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.
相关文献
Selective conversion of lignin in corncob residue to monophenols with high yield and selectivity
Zhicheng Jiang, Ting He, Jianmei Li, Changwei Hu
DOI: 10.1039/C4GC00620H
Evaluating water miscible deep eutectic solvents (DESs) and ionic liquids as potential lubricants
Andrew P. Abbott, Robert C. Harris, Karl S. Ryder
DOI: 10.1039/C4GC00952E
Catalyst-free sulfonylation of activated alkenes for highly efficient synthesis of mono-substituted ethyl sulfones in water
Yu Yang, Lin Tang, Sheng Zhang, Xuefeng Guo, Zhenggen Zha, Zhiyong Wang
DOI: 10.1039/C4GC00932K
t-BuXPhos: a highly efficient ligand for Buchwald–Hartwig coupling in water
Patrick Wagner, Maud Bollenbach, Christelle Doebelin, Frédéric Bihel, Jean-Jacques Bourguignon, Martine Schmitt
DOI: 10.1039/C4GC00853G
Influence of precursor type on non-toxic hybrid inks for high-efficiency Cu2ZnSnS4 thin-film solar cells
Kyujin Kim, Inhyuk Kim, Yunjung Oh, Daehee Lee, Kyoohee Woo, Sunho Jeong, Jooho Moon
DOI: 10.1039/C4GC00896K
Total photocatalysis conversion from cyclohexane to cyclohexanone by C3N4/Au nanocomposites
Juan Liu, Yanmei Yang, Naiyun Liu, Yang Liu, Hui Huang, Zhenhui Kang
DOI: 10.1039/C4GC01126K
Rational investigations in the ring opening of cyclic carbonates by amines
L. Jean-Gérard, R. Auvergne, D. Benazet, S. Caillol, B. Andrioletti
DOI: 10.1039/C4GC01032A
Comprehensive mass analysis for chemical processes, a case study on l-Dopa manufacture
Tao Li, Xuan Li
DOI: 10.1039/C4GC00565A
Correction: Catalytic aerobic oxidation of renewable furfural to maleic anhydride and furanone derivatives with their mechanistic studies
Jihong Lan, Zhuqi Chen, Jinchi Lin, Guochuan Yin
DOI: 10.1039/C4GC90039A
您可能还喜欢
N-2,2-丙烯基-2-丙烯酰胺(CAS号:2555-13-7)通常如何合成?
N-2,2-丙烯基-2-丙烯酰胺通常通过丙烯酰胺与丙烯基卤化物的缩合反应合成。该反应通常在温和的条件下进行,使用适量的碱如吡啶作为催化剂。反应的选择性良好,产率...
什么是1,2-二碘四氟代乙烷(CAS号:354-65-4)?
1,2-二碘四氟代乙烷是一种有机化合物,化学式为C2F4I2,CAS号为354-65-4。它是一种无色透明液体,具有特殊的化学性质和物理性质,包括高沸点、低挥发...
3-溴-1H-吡咯[3,2-c]吡啶-4-碳腈(CAS号:1000341-71-8)适用哪些法规指南?
根据GHS(全球化学品统一分类和标签制度),3-溴-1H-吡咯[3,2-c]吡啶-4-碳腈被归类为第2类易燃液体。在欧盟,该化合物需要符合REACH法规的要求,...
1-氯甲基萘磺酸(CAS号:87491-79-0)安全吗?
1-氯甲基萘磺酸在使用时需要谨慎,因为它具有一定的刺激性和腐蚀性。操作时应佩戴适当的防护装备,如防化服、手套、护目镜等,避免直接接触皮肤和吸入其蒸汽。
二氯(二环戊二烯)铂(CAS号:12083-92-0)的主要用途是什么?
该化合物主要用于催化剂领域,特别是在有机合成中的催化氧化反应以及作为某些药物合成的中间体。此外,它还被研究用于纳米材料的制备。
3-溴-7-氯噻吩并[3,2-b]吡啶-6-甲腈(CAS号:798574-82-0)安全吗?
3-溴-7-氯噻吩并[3,2-b]吡啶-6-甲腈在处理时需要谨慎,因其含有溴和氯等强卤素,可能具有一定的刺激性和腐蚀性。使用时应佩戴适当的个人防护装备,避免皮肤...
(R)-1-((R)-2-(2’-二环己基膦苯基)三戊铁基]乙基(双-3,5-三氟甲基苯基)膦(CAS号:494227-32-6)的主要用途是什么?
该化合物主要用于有机合成领域,特别是作为催化剂或配体,在有机合成反应中发挥重要作用。此外,它还可能应用于催化加氢反应、偶联反应等。
3-[6-(Diphenylphosphoryl)-2-naphthyl]-1,10-phenanthroline(CAS号:1480371-38-7)安全吗?
3-[6-(Diphenylphosphoryl)-2-naphthyl]-1,10-phenanthroline在正常使用条件下相对安全,但在操作时应穿戴适当...
在合成中是否有ETHYL 2-(4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)CYCLOHEX-3-ENYL)ACETATE(CAS号:1166829-70-4)的替代品?
可以考虑使用类似结构的化合物作为替代品,如2-(4-环戊基环己烯基)乙酸酯,这种化合物在结构上相似,可能在某些合成路径中作为替代品。
如何处理含有3-(3-氨基丙基)丙酮缩甘油(CAS号:131606-42-3)的废料?
处理含有3-(3-氨基丙基)丙酮缩甘油的废料时,首先应确保遵守当地的环保法规。对于危险废物,应进行分类收集,然后送至专业的废物处理设施进行焚烧或安全填埋。在处理...
来源期刊
Organic & Biomolecular Chemistry

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.














![3-[(3R,4R)-3-[(6-aminopyrimidin-4-yl)-methyl-amino]-4-methyl-1-piperidyl]-3-oxo-propanenitrile structure 3-[(3R,4R)-3-[(6-aminopyrimidin-4-yl)-methyl-amino]-4-methyl-1-piperidyl]-3-oxo-propanenitrile structure](https://cnstatic.chemtradehub.com/structs/164/1640971-60-3-83a4.webp)