Microwave-assisted solid phase synthesis, PEGylation, and biological activity studies of glucagon-like peptide-1(7-36) amide.
The insulinotropic hormone glucagon-like peptide-1 (GLP-1) is rapidly inactivated in the body. In order to improve its stability, we replaced the enzymatic hydrolyzation position Ala(8)with Gly and replaced Ala(30) with Cys firstly. Then the modified peptide was further PEGylated at thiol group of Cys(30). Biological activity studies showed that the resulting mPEG-MAL-Gly(8)-Cys(30)-GLP-1(7-36)-NH(2) exhibited long-lasting effect while maintaining moderate glucose-lowering activity.
Chi
Yushi
Y
Center of Drug Research, China Pharmaceutical University, Nanjing 210009, China.
Zhang
Huibin
H
Huang
Wenlong
W
Zhou
Jinpei
J
Zhou
Yinghong
Y
Qian
Hai
H
Ni
Shuaijian
S
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008872:Microwaves; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010446:Peptide Fragments; D011092:Polyethylene Glycols; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4