کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1987131 1540293 2010 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structural binding evidence of the trypanocidal drugs Berenil® and Pentacarinate® active principles to a serine protease model
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Structural binding evidence of the trypanocidal drugs Berenil® and Pentacarinate® active principles to a serine protease model
چکیده انگلیسی

Bovine trypsin is a model system for the serine protease class of enzymes, which is an important target for contemporary medicinal chemistry. Some structural and thermodynamic reports are available on its interaction with benzamidine-based compounds but no structural information is available so far on its binding modes to the active principles of the trypanocidal drugs Pentacarinate® (pentamidine) and Berenil® (diminazene). The crystallographic structures of bovine β-trypsin in complex with the ligands were determined to a resolution of 1.57 Å (diminazene) and 1.70 Å (diminazene and pentamidine). The second benzamidine moieties in these inhibitors are bound to the enzyme in different hot spots and only few hydrogen bonds mediate these interactions. Thermodynamic parameters for the association of pentamidine with β-trypsin reveal that this inhibitor has about 1.3-fold lower affinity than diminazene. Moreover its binding mode resembles other benzamidine-based compounds that assess the aryl binding pocket of the enzyme; however, with almost 2.5-fold higher affinity. This is the first structural evidence of the binding of Berenil® and Pentacarinate® active principles trypanocidal drugs to serine proteases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 46, Issue 5, 1 June 2010, Pages 502–511
نویسندگان
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