PMID- 26727558
OWN - NLM
STAT- MEDLINE
DCOM- 20161026
LR  - 20240325
IS  - 1554-8937 (Electronic)
IS  - 1554-8929 (Print)
IS  - 1554-8929 (Linking)
VI  - 11
IP  - 2
DP  - 2016 Feb 19
TI  - Design of Potent and Proteolytically Stable Oxyntomodulin Analogs.
PG  - 324-8
LID - 10.1021/acschembio.5b00787 [doi]
AB  - Incretin-based peptides are effective therapeutics for treating type 2 diabetes 
      mellitus (T2DM). Oxyntomodulin (OXM), a dual agonist of GLP-1R and GCGR, has 
      shown superior weight loss and glucose lowering effects, compared to single 
      GLP-1R agonists. To overcome the short half-life and rapid renal clearance of 
      OXM, which limit its therapeutic potential, both lipid and PEG modified OXM 
      analogs have been reported. However, these approaches often result in reduced 
      potency or PEG-associated toxicity. Herein, we report a new class of cross-linked 
      OXM analogs that show increased plasma stability and higher potency in activating 
      both GLP-1R and GCGR. Moreover, the extended in vivo half-life results in 
      superior antihyperglycemic activity in mice compared to the wild-type OXM.
FAU - Muppidi, Avinash
AU  - Muppidi A
AD  - California Institute for Biomedical Research (Calibr) , 11119 North Torrey Pines 
      Road, La Jolla, California 92037, United States.
AD  - Department of Chemistry, State University of New York at Buffalo , Buffalo, New 
      York 14260-3000, United States.
FAU - Zou, Huafei
AU  - Zou H
AD  - California Institute for Biomedical Research (Calibr) , 11119 North Torrey Pines 
      Road, La Jolla, California 92037, United States.
FAU - Yang, Peng Yu
AU  - Yang PY
AD  - Department of Chemistry, The Scripps Research Institute , 10550 North Torrey 
      Pines Road, La Jolla, California 92037, United States.
FAU - Chao, Elizabeth
AU  - Chao E
AD  - California Institute for Biomedical Research (Calibr) , 11119 North Torrey Pines 
      Road, La Jolla, California 92037, United States.
FAU - Sherwood, Lance
AU  - Sherwood L
AD  - California Institute for Biomedical Research (Calibr) , 11119 North Torrey Pines 
      Road, La Jolla, California 92037, United States.
FAU - Nunez, Vanessa
AU  - Nunez V
AD  - California Institute for Biomedical Research (Calibr) , 11119 North Torrey Pines 
      Road, La Jolla, California 92037, United States.
FAU - Woods, Ashley K
AU  - Woods AK
AD  - California Institute for Biomedical Research (Calibr) , 11119 North Torrey Pines 
      Road, La Jolla, California 92037, United States.
FAU - Schultz, Peter G
AU  - Schultz PG
AD  - California Institute for Biomedical Research (Calibr) , 11119 North Torrey Pines 
      Road, La Jolla, California 92037, United States.
AD  - Department of Chemistry, The Scripps Research Institute , 10550 North Torrey 
      Pines Road, La Jolla, California 92037, United States.
FAU - Lin, Qing
AU  - Lin Q
AD  - Department of Chemistry, State University of New York at Buffalo , Buffalo, New 
      York 14260-3000, United States.
FAU - Shen, Weijun
AU  - Shen W
AD  - California Institute for Biomedical Research (Calibr) , 11119 North Torrey Pines 
      Road, La Jolla, California 92037, United States.
LA  - eng
GR  - R01 GM085092/GM/NIGMS NIH HHS/United States
GR  - GM 085092/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160104
PL  - United States
TA  - ACS Chem Biol
JT  - ACS chemical biology
JID - 101282906
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Oxyntomodulin)
RN  - 0 (Receptors, Glucagon)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cross-Linking Reagents/chemistry/pharmacokinetics/pharmacology
MH  - Glucagon-Like Peptide-1 Receptor/*agonists/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Hypoglycemic Agents/blood/*chemistry/*pharmacology
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Oxyntomodulin/blood/*chemistry/*pharmacology
MH  - Proteolysis
MH  - Receptors, Glucagon/*agonists/metabolism
PMC - PMC4861236
MID - NIHMS783386
EDAT- 2016/01/05 06:00
MHDA- 2016/10/27 06:00
PMCR- 2017/02/19
CRDT- 2016/01/05 06:00
PHST- 2016/01/05 06:00 [entrez]
PHST- 2016/01/05 06:00 [pubmed]
PHST- 2016/10/27 06:00 [medline]
PHST- 2017/02/19 00:00 [pmc-release]
AID - 10.1021/acschembio.5b00787 [doi]
PST - ppublish
SO  - ACS Chem Biol. 2016 Feb 19;11(2):324-8. doi: 10.1021/acschembio.5b00787. Epub 
      2016 Jan 4.