Design of stapled oxyntomodulin analogs containing functionalized biphenyl cross-linkers

Yulin Tian; Huafei Zou; Peng An; Zhihong Zhou; Weijun Shen; Qing Lin

doi:10.1016/j.tet.2018.11.060

Design of stapled oxyntomodulin analogs containing functionalized biphenyl cross-linkers

Yulin Tian
, Huafei Zou
, Peng An
, Zhihong Zhou
, Weijun Shen
, Qing Lin

Chemistry

SUNY Buffalo
Baird Research Park
Scripps Research Institute

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English
Pages (from-to)	286-295
Number of pages	10
Journal	Tetrahedron
Volume	75
Issue number	2
DOIs	https://doi.org/10.1016/j.tet.2018.11.060
State	Published - Jan 11 2019

Keywords

Cross-linker
Dual agonist
GCGR
GLP-1R
Oxyntomodulin

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10.1016/j.tet.2018.11.060

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title = "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.",

keywords = "Cross-linker, Dual agonist, GCGR, GLP-1R, Oxyntomodulin",

author = "Yulin Tian and Huafei Zou and Peng An and Zhihong Zhou and Weijun Shen and Qing Lin",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",

year = "2019",

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doi = "10.1016/j.tet.2018.11.060",

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T1 - Design of stapled oxyntomodulin analogs containing functionalized biphenyl cross-linkers

AU - Tian, Yulin

AU - Zou, Huafei

AU - An, Peng

AU - Zhou, Zhihong

AU - Shen, Weijun

AU - Lin, Qing

PY - 2019/1/11

Y1 - 2019/1/11

N2 - 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.

AB - 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.

KW - Cross-linker

KW - Dual agonist

KW - GCGR

KW - GLP-1R

KW - Oxyntomodulin

UR - https://www.scopus.com/pages/publications/85057887723

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DO - 10.1016/j.tet.2018.11.060

M3 - Article

AN - SCOPUS:85057887723

SN - 0040-4020

VL - 75

SP - 286

EP - 295

JO - Tetrahedron

JF - Tetrahedron

IS - 2

ER -

Design of stapled oxyntomodulin analogs containing functionalized biphenyl cross-linkers

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Keywords

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