6YKC

Metala-Carborane di-ethyl-sulfonamide (trans isomer) in complex with CA IX mimic

6YKC の概要

• エントリーDOI: 10.2210/pdb6ykc/pdb
• 関連するPDBエントリー: 6Y3J
• 分子名称: Carbonic anhydrase 2, ZINC ION, Metala-Carborane di-ethyl-sulfonamide, ... (5 entities in total)
• 機能のキーワード: carbonic anhydrase, ca inhibitor, lyase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30302.00

構造登録者

Kugler, M.,Brynda, J.,Pospisilova, K.,Rezacova, P. (登録日: 2020-04-06, 公開日: 2020-09-09, 最終更新日: 2024-01-24)

主引用文献

Gruner, B.,Kugler, M.,El Anwar, S.,Holub, J.,Nekvinda, J.,Bavol, D.,Ruzickova, Z.,Pospisilova, K.,Fabry, M.,Kral, V.,Brynda, J.,Rezacova, P.
Cobalt Bis(dicarbollide) Alkylsulfonamides: Potent and Highly Selective Inhibitors of Tumor Specific Carbonic Anhydrase IX.
Chempluschem, 86:352-363, 2021

PubMed Abstract: Carbonic anhydrase IX (CAIX) is an enzyme expressed on the surface of cells in hypoxic tumors. It plays a role in regulation of tumor pH and promotes thus tumor cell survival and occurrence of metastases. Here, derivatives of the cobalt bis(dicarbollide)(1-) anion are reported that are based on substitution at the carbon sites of the polyhedra by two alkylsulfonamide groups differing in the length of the aliphatic connector (from C1 to C4, n=1-4), which were prepared by cobalt insertion into the 7-sulfonamidoalkyl-7,8-dicarba-nido-undecaborate ions. Pure meso- and rac-diastereoisomeric forms were isolated. The series is complemented with monosubstituted species (n=2). Synthesis by a direct method furnished similar derivatives (n=2, 3), which are chlorinated at the B(8,8') boron sites. All compounds inhibited CAIX with subnanomolar inhibition constants and showed high selectivity for CAIX. The best inhibitory properties were observed for the compound with n= 3 and two substituents present in rac-arrangement with K =20 pM and a selectivity index of 668. X-ray crystallography was used to study interactions of these compounds with the active site of CAIX on the structural level.

PubMed: 32955786
DOI: 10.1002/cplu.202000574

実験手法

X-RAY DIFFRACTION (1.2 Å)