PMID- 33049303
OWN - NLM
STAT- MEDLINE
DCOM- 20210607
LR  - 20240226
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 890
DP  - 2021 Jan 5
TI  - Albumin-binding domain extends half-life of glucagon-like peptide-1.
PG  - 173650
LID - S0014-2999(20)30742-1 [pii]
LID - 10.1016/j.ejphar.2020.173650 [doi]
AB  - Glucagon-like peptide-1 (GLP-1) is considered to be a promising peptide for the 
      treatment of type 2 diabetes mellitus (T2DM). However, the extremely short 
      half-life of GLP-1 limits its clinical application. Albumin-binding domain (ABD) 
      with high affinity for human serum albumin (HSA) has been used widely for 
      half-life extension of therapeutic peptides and proteins. In the present study, 
      novel GLP-1 receptor agonists were designed by genetic fusion of GLP-1 to three 
      kinds of ABDs with different affinities for HSA: GA3, ABD035 and ABDCon. The 
      bioactivities and half-lives of ABD-fusion GLP-1 proteins with different types 
      and lengths of linkers were investigated in vitro and in vivo. The results 
      demonstrated that ABD-fusion GLP-1 proteins could bind to HSA with high affinity. 
      The blood glucose-lowering effect of GLP-1 was significantly improved and 
      sustained by fusion to ABD. Meanwhile, the fusion proteins significantly 
      inhibited food intake, which was beneficial for T2DM and obesity treatment. The 
      half-life of GLP-1 was substantially extended by virtue of ABD. The in vivo 
      results also showed that a longer linker inserted between GLP-1 and ABD resulted 
      in a higher blood glucose-lowering effect. The fusion proteins generated by 
      fusion of GLP-1 to GA3, ABD035 and ABDCon exhibited similar bioactivities and 
      pharmacokinetics in vivo. These findings demonstrate that ABD-fusion GLP-1 
      proteins retain the bioactivities of natural GLP-1 and can be further developed 
      for T2DM treatment and weight loss. It also indicates that the ABD-fusion 
      strategy can be generally applicable to any peptide or protein, to improve 
      pharmacodynamic and pharmacokinetic properties.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Tan, Huanbo
AU  - Tan H
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
FAU - Su, Wencheng
AU  - Su W
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
FAU - Zhang, Wenyu
AU  - Zhang W
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
FAU - Zhang, Jie
AU  - Zhang J
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
FAU - Sattler, Michael
AU  - Sattler M
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; Institute 
      of Structural Biology, Helmholtz Zentrum Munchen, German Research Center for 
      Environmental Health, Neuherberg, Germany; Center for Integrated Protein Science 
      Munich at Chair Biomolecular NMR Spectroscopy, Department Chemie, Technische 
      Universitat Munchen, Garching, Germany.
FAU - Zou, Peijian
AU  - Zou P
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; Institute 
      of Structural Biology, Helmholtz Zentrum Munchen, German Research Center for 
      Environmental Health, Neuherberg, Germany; Center for Integrated Protein Science 
      Munich at Chair Biomolecular NMR Spectroscopy, Department Chemie, Technische 
      Universitat Munchen, Garching, Germany. Electronic address: peijian.zou@tum.de.
LA  - eng
PT  - Journal Article
DEP - 20201010
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Anti-Obesity Agents)
RN  - 0 (Blood Glucose)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - ZIF514RVZR (Serum Albumin, Human)
SB  - IM
MH  - Animals
MH  - Anti-Obesity Agents/chemistry/*pharmacokinetics/pharmacology
MH  - Blood Glucose/drug effects
MH  - Diabetes Mellitus, Type 2/drug therapy
MH  - Eating/drug effects
MH  - Female
MH  - Glucagon-Like Peptide 1/chemistry/*pharmacokinetics/pharmacology
MH  - Glucagon-Like Peptide-1 Receptor/agonists
MH  - Glucose Tolerance Test
MH  - Half-Life
MH  - Humans
MH  - Hypoglycemic Agents/chemistry/*pharmacokinetics/pharmacology
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Protein Binding
MH  - Protein Domains
MH  - Recombinant Fusion Proteins/chemistry/*pharmacokinetics/pharmacology
MH  - Serum Albumin, Human/*metabolism
MH  - Mice
OTO - NOTNLM
OT  - ABD035
OT  - ABDCon
OT  - Bioactivity
OT  - GA3
OT  - Glucagon-like peptide-1
OT  - Half-life extension
EDAT- 2020/10/14 06:00
MHDA- 2021/06/08 06:00
CRDT- 2020/10/13 20:09
PHST- 2020/05/22 00:00 [received]
PHST- 2020/10/05 00:00 [revised]
PHST- 2020/10/09 00:00 [accepted]
PHST- 2020/10/14 06:00 [pubmed]
PHST- 2021/06/08 06:00 [medline]
PHST- 2020/10/13 20:09 [entrez]
AID - S0014-2999(20)30742-1 [pii]
AID - 10.1016/j.ejphar.2020.173650 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2021 Jan 5;890:173650. doi: 10.1016/j.ejphar.2020.173650. Epub 
      2020 Oct 10.