کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2186057 1096031 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Adding a Lysine Mimic in the Design of Potent Inhibitors of Histone Lysine Methyltransferases
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Adding a Lysine Mimic in the Design of Potent Inhibitors of Histone Lysine Methyltransferases
چکیده انگلیسی

Dynamic histone lysine methylation involves the activities of modifying enzymes (writers), enzymes removing modifications (erasers), and readers of the histone code. One common feature of these activities is the recognition of lysines in methylated and unmethylated states, whether they are substrates, reaction products, or binding partners. We applied the concept of adding a lysine mimic to an established inhibitor (BIX-01294) of histone H3 lysine 9 methyltransferases G9a and G9a-like protein by including a 5-aminopentyloxy moiety, which is inserted into the target lysine-binding channel and becomes methylated by G9a-like protein, albeit slowly. The compound enhances its potency in vitro and reduces cell toxicity in vivo. We suggest that adding a lysine or methyl-lysine mimic should be considered in the design of small-molecule inhibitors for other methyl-lysine writers, erasers, and readers.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 400, Issue 1, 2 July 2010, Pages 1–7
نویسندگان
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