PMID- 32510929
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20210621
IS  - 1520-4812 (Electronic)
IS  - 1043-1802 (Linking)
VI  - 31
IP  - 7
DP  - 2020 Jul 15
TI  - Zwitterionic Polymer Conjugated Glucagon-like Peptide-1 for Prolonged Glycemic 
      Control.
PG  - 1812-1819
LID - 10.1021/acs.bioconjchem.0c00286 [doi]
AB  - Glucagon-like peptide-1 (GLP-1) is of particular interest for treating type 2 
      diabetes mellitus (T2DM), as it induces insulin secretion in a glucose-dependent 
      fashion and has the potential to facilitate weight control. However, native GLP-1 
      is a short incretin peptide that is susceptible to fast proteolytic inactivation 
      and rapid clearance from the circulation. Various GLP-1 analogs and 
      bioconjugation of GLP-1 analogs have been developed to counter these issues, but 
      these modifications are frequently accompanied by the sacrifice of potency and 
      the induction of immunogenicity. Here, we demonstrated that with the conjugation 
      of a zwitterionic polymer, poly(carboxybetaine) (pCB), the pharmacokinetic 
      properties of native GLP-1 were greatly enhanced without serious negative effects 
      on its potency and secondary structure. The pCB conjugated GLP-1 further provided 
      glycemic control for up to 6 days in a mouse study. These results illustrate that 
      the conjugation of pCB could realize the potential of using native GLP-1 for 
      prolonged glycemic control in treating T2DM.
FAU - Tsao, Caroline
AU  - Tsao C
AUID- ORCID: 0000-0001-5815-4035
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
FAU - Yuan, Zhefan
AU  - Yuan Z
AUID- ORCID: 0000-0002-4724-6214
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
FAU - Dong, Dianyu
AU  - Dong D
AUID- ORCID: 0000-0002-2293-7959
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
AD  - School of Chemical Engineering and Technology and Key Laboratory of Systems 
      Bioengineering of Ministry of Education, Tianjin University, Tianjin, 300350, 
      China.
FAU - Wu, Kan
AU  - Wu K
AUID- ORCID: 0000-0002-8900-5574
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
FAU - Niu, Liqian
AU  - Niu L
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
FAU - McMullen, Patrick
AU  - McMullen P
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
FAU - Luozhong, Sijin
AU  - Luozhong S
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
FAU - Hung, Hsiang-Chieh
AU  - Hung HC
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
FAU - Cheng, Yu-Hong
AU  - Cheng YH
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
FAU - Jiang, Shaoyi
AU  - Jiang S
AUID- ORCID: 0000-0001-9863-6899
AD  - Department of Chemical Engineering, University of Washington, Seattle, Washington 
      98195, United States.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200619
PL  - United States
TA  - Bioconjug Chem
JT  - Bioconjugate chemistry
JID - 9010319
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Polymers)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*blood/drug therapy
MH  - Disease Models, Animal
MH  - Glucagon-Like Peptide 1/*chemistry/pharmacokinetics/therapeutic use
MH  - Glycemic Control/*methods
MH  - Half-Life
MH  - Hypoglycemic Agents/pharmacokinetics/*therapeutic use
MH  - Mice
MH  - Polymers/*chemistry
MH  - Protein Structure, Secondary
EDAT- 2020/06/09 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/06/09 06:00
PHST- 2020/06/09 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/06/09 06:00 [entrez]
AID - 10.1021/acs.bioconjchem.0c00286 [doi]
PST - ppublish
SO  - Bioconjug Chem. 2020 Jul 15;31(7):1812-1819. doi: 
      10.1021/acs.bioconjchem.0c00286. Epub 2020 Jun 19.