含功能化联苯交联剂的钉合胃泌酸调节素类似物的设计
Design of Stapled Oxyntomodulin Analogs Containing Functionalized Biphenyl Cross-Linkers.
作者信息
Tian Yulin, Zou Huafei, An Peng, Zhou Zhihong, Shen Weijun, Lin Qing
机构信息
Department of Chemistry, State University of New York at Buffalo, Buffalo, New York 14260, United States.
Transira Therapeutics, 1576 Sweet Home Road, Baird Research Park, Amherst, New York 14228, United States.
出版信息
Tetrahedron. 2019 Jan 11;75(2):286-295. doi: 10.1016/j.tet.2018.11.060. Epub 2018 Nov 28.
A panel of three lipid-modified, functionalized biphenyl cross-linkers (fBph) were synthesized and subsequently employed in the preparation of the stapled oxyntomodulin (OXM) analogs. In a luciferase-based reporter assay, these stapled OXM analogs showed varying degree of potency in activating GLP-1R and GCGR, presumably due to the disparate effect of the lipid chains on the local environment close to the ligand-receptor binding interface. In particular, the fBph-1 cross-linked peptide with the lipid chain attached to position-3 of the biphenyl cross-linker exhibited the highest dual agonist activity.
合成了一组三种脂质修饰的、功能化的联苯交联剂（fBph），随后将其用于制备带钉的胃泌酸调节素（OXM）类似物。在基于荧光素酶的报告基因检测中，这些带钉的OXM类似物在激活胰高血糖素样肽-1受体（GLP-1R）和胰高血糖素受体（GCGR）方面表现出不同程度的效力，这可能是由于脂质链对靠近配体-受体结合界面的局部环境有不同的影响。特别是，在联苯交联剂的3位连接脂质链的fBph-1交联肽表现出最高的双重激动剂活性。
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