PMID- 35500009
OWN - NLM
STAT- MEDLINE
DCOM- 20220504
LR  - 20220716
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 17
IP  - 5
DP  - 2022
TI  - A novel strategy for production of liraglutide precursor peptide and development 
      of a new long-acting incretin mimic.
PG  - e0266833
LID - 10.1371/journal.pone.0266833 [doi]
LID - e0266833
AB  - Nowadays, a small number of incretin mimics are used to treat type 2 diabetes 
      mellitus (T2DM) due to their longer half-life. The present study aimed to 
      introduce a novel method for producing the liraglutide precursor peptide (LPP) 
      and developing a potentially new incretin mimic. Here, human alphaB-crystallin 
      (alphaB-Cry) was ligated to the LPP at the gene level, and the gene construct was 
      expressed in Escherichia coli with a relatively good efficiency. The hybrid 
      protein (alphaB-lir) was then purified by a precipitation method followed by anion 
      exchange chromatography. After that, the peptide was released from the carrier 
      protein by a chemical cleavage method yielding about 70%. The LPP was then 
      purified by gel filtration chromatography, and HPLC estimated its purity to be 
      about 98%. Also, the molecular mass of the purified peptide was finally confirmed 
      by mass spectroscopy analysis. Assessment of the secondary structures suggested a 
      dominant alpha-helical structure for the LPP and a beta-sheet rich structure for the 
      hybrid protein. The subcutaneous injection of the LPP and the alphaB-lir hybrid 
      protein significantly reduced the blood sugar levels in healthy and diabetic mice 
      and stimulated insulin secretion. Also, the hybrid protein exerts its 
      bioactivities more effectively than the LPP over a relatively longer period of 
      time. The results of this study suggested a novel method for the easy and 
      cost-effective production of the LPP and introduced a new long-acting incretin 
      mimic that can be potentially used for the treatment of T2DM patients.
FAU - Ahmadi, Samaneh
AU  - Ahmadi S
AD  - Department of Biology, Protein Chemistry Laboratory (PCL), College of Sciences, 
      Shiraz University, Shiraz, Iran.
FAU - Shahsavani, Mohammad Bagher
AU  - Shahsavani MB
AUID- ORCID: 0000-0002-4651-7975
AD  - Department of Biology, Protein Chemistry Laboratory (PCL), College of Sciences, 
      Shiraz University, Shiraz, Iran.
FAU - Tavaf, Zohreh
AU  - Tavaf Z
AD  - Department of Biology, Protein Chemistry Laboratory (PCL), College of Sciences, 
      Shiraz University, Shiraz, Iran.
FAU - Albaghlany, Rawayh Muslim
AU  - Albaghlany RM
AD  - Department of Biology, Protein Chemistry Laboratory (PCL), College of Sciences, 
      Shiraz University, Shiraz, Iran.
FAU - Kumar, Ashutosh
AU  - Kumar A
AD  - Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai, India.
FAU - Moosavi-Movahedi, Ali Akbar
AU  - Moosavi-Movahedi AA
AD  - Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, 
      Iran.
FAU - Yousefi, Reza
AU  - Yousefi R
AUID- ORCID: 0000-0001-7396-7720
AD  - Department of Biology, Protein Chemistry Laboratory (PCL), College of Sciences, 
      Shiraz University, Shiraz, Iran.
AD  - Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, 
      Iran.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220502
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Incretins)
RN  - 0 (Peptides)
RN  - 839I73S42A (Liraglutide)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Experimental
MH  - *Diabetes Mellitus, Type 2/drug therapy/genetics
MH  - Humans
MH  - Incretins
MH  - Liraglutide
MH  - Mice
MH  - Peptides/chemistry
PMC - PMC9060347
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/05/03 06:00
MHDA- 2022/05/06 06:00
PMCR- 2022/05/02
CRDT- 2022/05/02 13:34
PHST- 2021/10/29 00:00 [received]
PHST- 2022/03/29 00:00 [accepted]
PHST- 2022/05/02 13:34 [entrez]
PHST- 2022/05/03 06:00 [pubmed]
PHST- 2022/05/06 06:00 [medline]
PHST- 2022/05/02 00:00 [pmc-release]
AID - PONE-D-21-34605 [pii]
AID - 10.1371/journal.pone.0266833 [doi]
PST - epublish
SO  - PLoS One. 2022 May 2;17(5):e0266833. doi: 10.1371/journal.pone.0266833. 
      eCollection 2022.