用于产生三角双锥配位几何结构的α-碳酸酐酶的双齿锌螯合剂。
Bidentate Zinc chelators for alpha-carbonic anhydrases that produce a trigonal bipyramidal coordination geometry.
机构信息
Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, 35032 Marburg, Germany.
出版信息
ChemMedChem. 2010 Sep 3;5(9):1609-15. doi: 10.1002/cmdc.201000200.
Abstract
A series of new zinc binding groups (ZBGs) has been evaluated kinetically on 13 carbonic anhydrase (CA) isoforms. The fragments show affinity for all isoforms with IC(50) values in the range of 2-11 microM. The crystal structure of hCA II in complex with one such fragment reveals a bidentate binding mode with a trigonal-bipyramidal coordination geometry at the Zn(2+) center. The fragment also interacts with Thr199 and Thr200 through hydrogen bonding and participates in a water network. Further development of this ZBG should increase the binding affinity leading to a structurally distinct and promising class of CA inhibitors.
摘要
已经对一系列新的锌结合基团 (ZBG) 进行了动力学评估，涉及 13 种碳酸酐酶 (CA) 同工酶。这些片段对所有同工酶均具有亲和力，IC 50 值在 2-11 μM 范围内。与其中一个片段形成复合物的 hCA II 的晶体结构揭示了 Zn(2+)中心的双齿结合模式和三角双锥配位几何形状。该片段还通过氢键与 Thr199 和 Thr200 相互作用，并参与水网络。进一步开发这种 ZBG 应该会提高结合亲和力，从而产生一类结构独特且有前途的 CA 抑制剂。
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本文引用的文献
1
Processing of X-ray diffraction data collected in oscillation mode.振荡模式下收集的X射线衍射数据的处理。
Methods Enzymol. 1997;276:307-26. doi: 10.1016/S0076-6879(97)76066-X.
2
The sulfamide motif in the design of enzyme inhibitors.磺胺基在酶抑制剂设计中的应用。
Expert Opin Ther Pat. 2006 Jan;16(1):27-47. doi: 10.1517/13543776.16.1.27.
3
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6
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J Biol Chem. 2008 Nov 7;283(45):30766-71. doi: 10.1074/jbc.M805353200. Epub 2008 Sep 2.
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