PMID- 32243177
OWN - NLM
STAT- MEDLINE
DCOM- 20220602
LR  - 20220603
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 17
IP  - 5
DP  - 2020 May 4
TI  - Ferritin-Displayed GLP-1 with Improved Pharmacological Activities and 
      Pharmacokinetics.
PG  - 1663-1673
LID - 10.1021/acs.molpharmaceut.0c00098 [doi]
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin (a type of metabolic hormone that 
      stimulates a decrease in blood glucose levels), holding great potential for the 
      treatment of type 2 diabetes mellitus (T2DM). However, its extremely short 
      half-life of 1-2 min hampers any direct clinical application. Here, we describe 
      the application of the heavy chain of human ferritin (HFt) nanocage as a carrier 
      to improve the pharmacological properties of GLP-1. The GLP-HFt was designed by 
      genetic fusion of GLP-1 to the N-terminus of HFt and was expressed in inclusion 
      bodies in E. coli. The refolding process was developed to obtain a soluble 
      GLP-HFt protein. The biophysical properties determined by size-exclusion 
      chromatography (SEC), dynamic light scattering (DLS), circular dichroism (CD), 
      transmission electron microscopy (TEM), and X-ray crystallography verified that 
      the GLP-HFt successfully formed a 24-mer nanocage with GLP-1 displayed on the 
      external surface of HFt. The in vivo pharmacodynamic results demonstrated that 
      the GLP-HFt nanocage retained the bioactivity of natural GLP-1, significantly 
      reduced the blood glucose levels for at least 24 h in a dose-dependent manner, 
      and inhibited food intake for at least 8-10 h. The half-life of the GLP-HFt 
      nanocage was approximately 52 h in mice after subcutaneous injection. The 
      prolonged half-life and sustained control of blood glucose levels indicate that 
      the GLP-HFt nanocage can be further developed for the treatment of T2DM. 
      Meanwhile, the HFt nanocage proves its great potential as a universal carrier 
      that improves the pharmacodynamic and pharmacokinetic properties of a wide range 
      of therapeutic peptides and proteins.
FAU - Su, Wencheng
AU  - Su W
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, 300308 Tianjin, China.
FAU - Tan, Huanbo
AU  - Tan H
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, 300308 Tianjin, China.
FAU - Janowski, Robert
AU  - Janowski R
AD  - Institute of Structural Biology, Helmholtz Zentrum Muenchen, German Research 
      Center for Environmental Health, 85764 Neuherberg, Germany.
FAU - Zhang, Wenyu
AU  - Zhang W
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, 300308 Tianjin, China.
FAU - Wang, Pengju
AU  - Wang P
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, 300308 Tianjin, China.
FAU - Zhang, Jie
AU  - Zhang J
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, 300308 Tianjin, China.
FAU - Zhai, Huanhuan
AU  - Zhai H
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, 300308 Tianjin, China.
FAU - Li, Jian
AU  - Li J
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, 300308 Tianjin, China.
FAU - Niessing, Dierk
AU  - Niessing D
AD  - Institute of Structural Biology, Helmholtz Zentrum Muenchen, German Research 
      Center for Environmental Health, 85764 Neuherberg, Germany.
AD  - Institute of Pharmaceutical Biotechnology, Ulm University, 89081 Ulm, Germany.
FAU - Sattler, Michael
AU  - Sattler M
AUID- ORCID: 0000-0002-1594-0527
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, 300308 Tianjin, China.
AD  - Institute of Structural Biology, Helmholtz Zentrum Muenchen, German Research 
      Center for Environmental Health, 85764 Neuherberg, Germany.
AD  - Center for Integrated Protein Science Munich at Chair Biomolecular NMR 
      Spectroscopy, Department Chemie, Technische Universitat Munchen, 85747 Garching, 
      Germany.
FAU - Zou, Peijian
AU  - Zou P
AUID- ORCID: 0000-0002-7561-8310
AD  - Industrial Enzymes National Engineering Laboratory, Tianjin Institute of 
      Industrial Biotechnology, Chinese Academy of Sciences, 300308 Tianjin, China.
AD  - Institute of Structural Biology, Helmholtz Zentrum Muenchen, German Research 
      Center for Environmental Health, 85764 Neuherberg, Germany.
AD  - Center for Integrated Protein Science Munich at Chair Biomolecular NMR 
      Spectroscopy, Department Chemie, Technische Universitat Munchen, 85747 Garching, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200413
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9007-73-2 (Ferritins)
SB  - IM
MH  - Animals
MH  - Blood Glucose
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Escherichia coli/metabolism
MH  - Ferritins
MH  - *Glucagon-Like Peptide 1/pharmacology
MH  - Hypoglycemic Agents/pharmacokinetics/pharmacology
MH  - Insulin/metabolism
MH  - Mice
OTO - NOTNLM
OT  - bioactivities
OT  - diabetes
OT  - ferritin
OT  - glucagon-like peptide-1
OT  - half-life
EDAT- 2020/04/04 06:00
MHDA- 2022/06/03 06:00
CRDT- 2020/04/04 06:00
PHST- 2020/04/04 06:00 [pubmed]
PHST- 2022/06/03 06:00 [medline]
PHST- 2020/04/04 06:00 [entrez]
AID - 10.1021/acs.molpharmaceut.0c00098 [doi]
PST - ppublish
SO  - Mol Pharm. 2020 May 4;17(5):1663-1673. doi: 10.1021/acs.molpharmaceut.0c00098. 
      Epub 2020 Apr 13.