7-Substituted pterins provide a new direction for ricin A chain inhibitors

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• 作者：Jeff M. Pruet ; Karl R. Jasheway ; Lawrence A. Manzano ; Yan Bai ; Eric V. Anslyn ; ^{anslyn@austin.utexas.edu} ; Jon D. Robertus ; ^{jrobertus@mail.utexas.edu}
• 关键词：Ricin inhibitors ; Pterin ; 7-Substituted derivatives ; Luciferase assay
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：September, 2011
• 年：2011
• 卷：46
• 期：9
• 页码：3608-3615
• 全文大小：1521 K

文摘

Ricin is a potent toxin found in castor seeds. The A chain, RTA, enzymaticlly depurinates a specific adenosine in ribosomal RNA, inhibiting protein synthesis. Ricin is a known chemical weapons threat having no effective antidote. This makes the discovery of new inhibitors of great importance. We have previously used 6-substituted pterins, such as pteroic acid, as an inhibitor platform with moderate success. We now report the success of 7-carboxy pterin (7CP) as an RTA inhibitor; its binding has been monitored using both kinetic and temperature shift assays and by X-ray crystallography. We also discuss the synthesis of various derivatives of 7CP, and their binding affinity and inhibitory effects, as part of a program to make effective RTA inhibitors.