期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 22, 期 37, 页码 13147-13155出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201602190
关键词
fullerenes; glycoconjugates; inhibitors; receptors; transferases
资金
- Fonds National de la Recherche Scientifique (FNRS, Mandat de Charge de Recherche) [PDR T.0170.13]
- China Scholarship Council (CSC) [201308520012]
The synthesis of unprecedented multimeric Kdo glycoclusters based on fullerene and calix[4] arene central scaffolds is reported. The compounds were used to study the mechanism and scope of multivalent glycosyltransferase inhibition. Multimeric mannosides based on porphyrin and pillar[5]arenes were also generated in a controlled manner. Twelve glycoclusters and their monomeric ligands were thus assayed against heptosyltransferase WaaC, which is an important bacterial glycosyltransferase that is involved in lipopolysaccharide biosynthesis. It was first found that all the multimers interact solely with the acceptor binding site of the enzyme even when the multimeric ligands mimic the heptose donor. Second, the novel Kdo glycofullerenes displayed very potent inhibition (K-i=0.14 mu m for the best inhibitor); an inhibition level rarely observed with glycosyltransferases. Although the observed multivalent effects (i.e., the enhancement of affinity of a ligand when presented in a multimeric fashion) were in general modest, a dramatic effect of the central scaffold on the inhibition level was evidenced: the fullerene and the porphyrin scaffolds being by far superior to the calix-and pillar-arenes. We could also show, by dynamic light scattering analysis, that the best inhibitor had the propensity to form aggregates with the heptosyltransferase. This aggregative property may contribute to the global multivalent enzyme inhibition, but probably do not constitute the main origin of inhibition.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据