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Design of Stapled Oxyntomodulin Analogs Containing Functionalized Biphenyl Cross-Linkers.

ABSTRACT: 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.

SUBMITTER: Tian Y

PROVIDER: S-EPMC6300064 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Design of Stapled Oxyntomodulin Analogs Containing Functionalized Biphenyl Cross-Linkers.

Tian Yulin Y Zou Huafei H An Peng P Zhou Zhihong Z Shen Weijun W Lin Qing Q

Tetrahedron 20181128 2

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 ...[more]

PMID: 30581241

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