کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1360633 981442 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Conformational analysis of trimeric maleimide substituted 1,5,9-triazacyclododecane HIV fusion scaffolds
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Conformational analysis of trimeric maleimide substituted 1,5,9-triazacyclododecane HIV fusion scaffolds
چکیده انگلیسی

An analysis of the conformational preferences of three trimeric maleimide substituted 1,5,9-triazacyclododecane derivatives, proposed as cross linking reagents for HIV-1 fusion inhibitors, is presented. Exhaustive sampling was performed using the mixed Low Mode Monte Carlo conformational searching technique on the corresponding OPLS2005/GBSA(water) potential energy surface. Geometric structure, molecular length, and hydrogen bonding patterns of the compounds are analyzed. Global minimum energy structures were verified as minima using B3LYP/6-31G∗ geometry optimization. All structures adopt a crown-like 12-membered ring conformation; however, the system with the shortest maleimide arms (1a) can also adopt alternative ring orientations. Overall, derivatives with longer maleimide arms were more flexible and resulted in ensembles with a larger number of low energy structures. Comparison with biological inhibition data indicates that there is very little relationship between molecular size and the ability of the scaffold to orient CD4M9 miniproteins for optimal inhibition; however hydrophobicity may play a role.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 3, 1 February 2009, Pages 1251–1258
نویسندگان
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