Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries.
Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries.
复制标题
DOI：
10.1039/c0ob00826e
复制
发表时间：
2011-03-07
影响因子：
3.2
通讯作者：
Field RA
中科院分区：
文献类型：
--
作者：
Harrison JA;Kartha KP;Fournier EJ;Lowary TL;Malet C;Nilsson UJ;Hindsgaul O;Schenkman S;Naismith JH;Field RA
克氏锥虫反式唾液酸酶是酶促α-2,3-唾液酸化反应的多功能催化剂。系统修饰的辛基半乳糖苷和辛基n -乙酰乳胺被评估为克氏t型反式唾液酸酶（TcTS）的抑制剂和底物，在探索其受体底物结合位点的背景下。这些研究表明，TcTS催化非还原端β-半乳糖残基的α-(2→3)-唾液化，对半乳糖2和4位的取代不耐受，而对半乳糖6位的取代耐受良好。进一步的研究表明，即使添加大块糖残基（葡萄糖，半乳糖）也不会对TcTS结合和转化产生负面影响，这突出了“内部”6-取代半乳糖残基作为TcTS受体底物的潜力。筛选的结果突出了一些结构特征（特别是咪唑和吲哚），值得在TcTS抑制剂开发的背景下进一步研究。
Trypanosoma cruzi trans-sialidase is a versatile catalyst for enzymatic α-2,3-sialylation reactions. Systematically modified octyl galactosides and octyl N-acetyllactosamines were assessed as inhibitors of, and substrates for, T. cruzi trans-sialidase (TcTS) in the context of exploring its acceptor substrate binding site. These studies show that TcTS, which catalyses the α-(2→3)-sialylation of non-reducing terminal β-galactose residues, is largely intolerant of substitution of the galactose 2 and 4 positions whereas substitution of the galactose 6 position is well tolerated. Further studies show that even the addition of a bulky sugar residue (glucose, galactose) does not impact negatively on TcTS binding and turnover, which highlights the potential of ‘internal’ 6-substituted galactose residues to serve as TcTS acceptor substrates. Results from screening a 93-membered thiogalactoside library highlight a number of structural features (notably imidazoles and indoles) that are worthy of further investigation in the context of TcTS inhibitor development.
登录
查看更多内容
影响因子：
16.6
作者：
Buchini, Sabrina;Buschiazzo, Alejandro;Withers, Stephen G.
通讯作者：
Withers, Stephen G.
影响因子：
8.4
作者：
Campo, Vanessa L.;Carvalho, Ivone;Field, Robert A.
通讯作者：
Field, Robert A.
影响因子：
15
作者：
Harris, R;Kiddle, GR;Homans, SW
通讯作者：
Homans, SW
影响因子：
3.5
作者：
Carvalho, Ivone;Andrade, Peterson;Field, Robert A.
通讯作者：
Field, Robert A.
影响因子：
2.9
作者：
Damager, Iben;Buchini, Sabrina;Withers, Stephen G.
通讯作者：
Withers, Stephen G.