کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1379098 982017 2006 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
CDK2/cyclinA inhibitors: Targeting the cyclinA recruitment site with small molecules derived from peptide leads
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
CDK2/cyclinA inhibitors: Targeting the cyclinA recruitment site with small molecules derived from peptide leads
چکیده انگلیسی

The syntheses of potent small molecule inhibitors of the CDK2/cyclinA recruitment site are described. Structure–activity trends of nanomolar octapeptides were examined through amino-acid substitution and truncation of the sequence resulting in the identification of a smaller, albeit significantly less potent, tetrapeptide lead. These losses in affinity were recovered by side-chain optimization and by rigidification of the peptide backbone using a combination of solid-phase parallel synthesis and structure-based design. Finally, two guanidine functionalities were replaced to improve drug-like properties, resulting in neutral small molecules equal in activity to that of the peptide lead.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 6, 15 March 2006, Pages 1716–1720
نویسندگان
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