کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1359793 981415 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
How to blast osteoblasts? Novel dicarba analogues of amylin-(1-8) to treat osteoporosis
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
How to blast osteoblasts? Novel dicarba analogues of amylin-(1-8) to treat osteoporosis
چکیده انگلیسی
When administered in vivo, amylin (1-8) stimulates osteoblast proliferation increasing bone volume and bone strength. The native cyclic octapeptide amylin (1-8) is unstable, however, it provides an attractive framework for the creation of more stable, orally active synthetic analogues using various peptidomimetic techniques. On-resin ring closing metathesis (RCM) on the olefinic side chains of allylglycine residues and lysine moieties functionalized with an allyloxycarbonyl (Alloc) group, was used to prepare novel carba-bridged surrogates of the disulfide bridge between Cys/2 and Cys/7 in amylin-(1-8). Commercially available Nα-Fmoc Nε-Alloc protected lysine was used as a convenient substrate for Grubbs' ring closing metathesis. Analogues of amylin-(1-8) prepared by cyclization of allylglycine residues that also contained proline residues at either position 4 or 6, or both, were also prepared to investigate the effect of proline as a 'kink-inducing' residue on the efficiency of the RCM reaction. Of the nine novel alkene-bridged analogues prepared, five showed promising biological activity in a proliferation study in primary foetal rat osteoblasts at physiological concentrations. Two of these analogues were chosen for further in vivo evaluation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 20, Issue 20, 15 October 2012, Pages 6011-6018
نویسندگان
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