کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1371937 981860 2010 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure-based design and synthesis of novel P2/P3 modified, non-peptidic β-secretase (BACE-1) inhibitors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Structure-based design and synthesis of novel P2/P3 modified, non-peptidic β-secretase (BACE-1) inhibitors
چکیده انگلیسی

Starting from peptidomimetic BACE-1 inhibitors, the P2 amino acid including the P2/P3 peptide bond was replaced by a rigid 3-aminomethyl cyclohexane carboxylic acid. Co-crystallization revealed an unexpected binding mode with the P3/P4 amide bond placed into the S3 pocket resulting in a new hydrogen bond interaction pattern. Further optimization based on this structure resulted in highly potent BACE-1 inhibitors with selectivity over BACE-2 and cathepsin D.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 6, 15 March 2010, Pages 1924–1927
نویسندگان
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