Microwave-assisted solid phase synthesis, PEGylation, and biological activity studies of glucagon-like peptide-1(7-36) amide

Yushi Chi; Huibin Zhang; Wenlong Huang; Jinpei Zhou; Yinghong Zhou; Hai Qian; Shuaijian Ni

doi:10.1016/j.bmc.2008.07.019

Microwave-assisted solid phase synthesis, PEGylation, and biological activity studies of glucagon-like peptide-1(7-36) amide

Bioorg Med Chem. 2008 Aug 15;16(16):7607-14. doi: 10.1016/j.bmc.2008.07.019. Epub 2008 Jul 12.

Authors

Yushi Chi¹, Huibin Zhang, Wenlong Huang, Jinpei Zhou, Yinghong Zhou, Hai Qian, Shuaijian Ni

Affiliation

¹ Center of Drug Research, China Pharmaceutical University, Nanjing 210009, China.

PMID: 18656368
DOI: 10.1016/j.bmc.2008.07.019

Abstract

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.

MeSH terms

Amino Acid Sequence
Animals
Blood Glucose / drug effects
Blood Glucose / metabolism
Dipeptidyl Peptidase 4 / metabolism
Glucagon-Like Peptide 1 / chemical synthesis
Glucagon-Like Peptide 1 / chemistry*
Glucagon-Like Peptide 1 / pharmacology
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / chemistry*
Hypoglycemic Agents / pharmacology
Male
Mice
Microwaves
Molecular Sequence Data
Peptide Fragments / chemical synthesis
Peptide Fragments / chemistry*
Peptide Fragments / pharmacology
Polyethylene Glycols / chemistry*
Spectrometry, Mass, Electrospray Ionization

Substances

Blood Glucose
Hypoglycemic Agents
Peptide Fragments
Polyethylene Glycols
Glucagon-Like Peptide 1
Dipeptidyl Peptidase 4