کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1396119 | 1501173 | 2011 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 7-Substituted pterins provide a new direction for ricin A chain inhibitors 7-Substituted pterins provide a new direction for ricin A chain inhibitors](/preview/png/1396119.png)
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.
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► Several new pterin compounds were synthesized and analyzed.
► Many compounds showed good inhibition of ricin toxin A in an in vitro assay.
► Nearly all of these compounds were observed through X-ray crystallography to be bound within the active site of RTA.
► The success of these compounds indicates a greater affinity of 7-substituted pterins, compared to the regioisomeric 6-derivatives.
Journal: European Journal of Medicinal Chemistry - Volume 46, Issue 9, September 2011, Pages 3608–3615