Synthesis and biological evaluation of glucagon-like peptide-1 analogs with the C-terminal helix 3 of albumin-binding domain 3.
Basic Information
ID: ALA5120806
Journal: Bioorg Med Chem
Title: Synthesis and biological evaluation of glucagon-like peptide-1 analogs with the C-terminal helix 3 of albumin-binding domain 3.
Authors: Zhang J, Li S, Dong Y, Tang H, He Y, Hu H, Feng J.
Abstract: Based on peptide 6 (Ser8-GLP-1 [7-35]-GVKALIDEILAA-NH2; GVKALI-DEILAA is the C-terminal helix 3 of albumin-binding domain 3 of protein G from bacterial Streptococcal G strain 148 [G148-ABD3]), a series of its analogs (compounds 0-VI: Aib8-GLP-1 [7-35]-linkers-GVKALIDEILAA-NH2) were designed and synthesized using microwave-assisted solid-phase synthesis. First, to monitor the reaction process and reduce potential risks, the synthesis process of compounds 0-VI was divided into three stages. Next, to explore the effect of these linkers on their albumin-binding rates, albumin-binding assays were performed. Finally, to evaluate their biological activities in vitro and in vivo, receptor potency, surface plasmon resonance (SPR), weight-loss, and glucose-lowering assays were carried out. These results indicated the linkers of different polarities between Aib8-GLP-1 (7-35) and the C-terminal helix 3 of ABD3 can significantly affect the albumin-binding rate of the C-terminal helix 3 of ABD3. And compound IV had the highest albumin-binding rates, weight-loss, and glucose-lowering effects among them.
CiteXplore: 35358863
DOI: 10.1016/j.bmc.2022.116725
Patent ID: ┄