کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1376003 981948 2005 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery of AICAR Tfase inhibitors that disrupt requisite enzyme dimerization
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery of AICAR Tfase inhibitors that disrupt requisite enzyme dimerization
چکیده انگلیسی

The discovery of a new class of aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) inhibitors through screening peptidomimetic libraries (>40,000 compounds) that act by inhibiting requisite enzyme dimerization is disclosed. In addition to defining key structural features of the lead compounds responsible for the activity, kinetic analysis of the remarkably small inhibitors established that they act as noncompetitive, dissociative inhibitors of AICAR Tfase with the prototypical lead (A1B3, Cappsin 1) exhibiting a Ki of 3.1 ± 0.3 μM. Thus, the studies define a unique approach to selectively targeting AICAR Tfase over all other folate-dependent enzymes, and it represents only one of a few enzymes for which inhibition achieved by disrupting requisite enzyme dimerization has emerged from screening unbiased combinatorial libraries.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 15, Issue 11, 2 June 2005, Pages 2840–2844
نویسندگان
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