کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361198 981458 2008 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Thiahomoisocitrate: A highly potent inhibitor of homoisocitrate dehydrogenase involved in the α-aminoadipate pathway
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Thiahomoisocitrate: A highly potent inhibitor of homoisocitrate dehydrogenase involved in the α-aminoadipate pathway
چکیده انگلیسی

Homoisocitrate dehydrogenase is involved in the α-aminoadipate pathway of l-lysine biosynthesis in higher fungi such as yeast and human pathogenic fungi. This enzyme catalyzes the oxidative decarboxylation of (2R,3S)-homoisocitrate into 2-ketoadipate using NAD+ as a coenzyme. A series of aza-, oxa-, and thia-analogues of homoisocitrate was designed and synthesized as an inhibitor for homoisocitrate dehydrogenase. Among them, thia-analogue showed strong competitive inhibitory activity as Ki = 97 nM toward homoisocitrate dehydrogenase derived from Saccharomyces cerevisiae. Kinetic studies suggested that the formation of the enolate intermediate played an important role in inhibition.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 6, 15 March 2008, Pages 3372–3376
نویسندگان
, ,