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

ABSTRACT: 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.

SUBMITTER: Pruet JM

PROVIDER: S-EPMC3164896 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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

Pruet Jeff M JM Jasheway Karl R KR Manzano Lawrence A LA Bai Yan Y Anslyn Eric V EV Robertus Jon D JD

European journal of medicinal chemistry 20110520 9

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 ...[more]

PMID: 21641093

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