کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5417783 | 1506958 | 2007 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A theoretical study of anthrax lethal factor inhibition by a set of novel carbamimidolyl-aryl-vinyl-carboxamidines: A possible mechanism involving zinc-ligation by amidine
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی تئوریک و عملی
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چکیده انگلیسی
A congeneric set of carbamimidolyl-aryl-vinyl-carboxamidines from the National Cancer Institute (NCI) open chemical repository were identified as potent inhibitors of anthrax lethal factor (LF), a zinc-dependent metalloprotease that plays a critical role in potentiating Bacillus anthracis infection. Surprisingly, these compounds exhibited no differential change in activity with concentration. Docking studies revealed that the indole-attached amidine substituents of these inhibitors were positioned in close proximity to the biological zinc atom and could potentially function as transition-state mimetics. This broaches the stunning possibility that the dose independence of these inhibitors is linked to zinc-ligation. Because the amidine functionality is highly basic and cationic, it is generally not considered a viable zinc-binding motif. However, quantum chemical calculations on small-molecule models predicted a marked decrease in the pKa of the amidine functionality when it is in close proximity to zinc, thus allowing for the formation of a robust zinc-amidine bond.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Structure: THEOCHEM - Volume 821, Issues 1â3, 1 November 2007, Pages 139-144
Journal: Journal of Molecular Structure: THEOCHEM - Volume 821, Issues 1â3, 1 November 2007, Pages 139-144
نویسندگان
Tam Luong Nguyen, Rekha G. Panchal, Igor A. Topol, Douglas Lane, Tara Kenny, James C. Burnett, Ann R. Hermone, Connor McGrath, Stanley K. Burt, Rick Gussio, Sina Bavari,