کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1360966 | 981453 | 2008 | 7 صفحه PDF | دانلود رایگان |
To elucidate the receptor-bound conformation of glucagon-like peptide-1 (GLP-1), a series of conformationally constrained GLP-1 analogues were synthesized by introducing lactam bridges between Lysi and Glui+4 to form α-helices at various positions. The activity and affinity of these analogues to GLP-1 receptors suggested that the receptor-bound conformation comprises two α-helical segments between residues 11-21 and 23-34. It is notable that the N-terminal α-helix is extended to Thr11, and that Gly22 plays a pivotal role in arranging the two α-helices. Based on these findings, a highly potent bicyclic GLP-1 analogue was synthesized which is the most conformationally constrained GLP-1 analogue reported to date.
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Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 23, 1 December 2008, Pages 10106–10112