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Synthesis and bioactivity evaluation of dipeptidyl peptidase IV resistant glucagon-like peptide-1 analogues
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نویسنده
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zhou j. ,ni s. ,zhang h. ,qian h. ,chi y. ,huang w. ,yu l. ,hu x. ,chen w.
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منبع
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protein and peptide letters - 2010 - دوره : 17 - شماره : 10 - صفحه:1290 -1295
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چکیده
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Glucagon-like peptide -1 (glp-1) is an incretin hormone displaying glucose-dependent stimulation of insulin secretion and trophic effects on the pancreatic β-cells. however,glp-1 is rapidly degraded to glp-1(9-36) by dipeptidyl peptidase-iv (dpp-iv),which removes the n-terminal dipeptide his7-ala8. the rapid inactivation of glp-1 in the blood circulation limits its clinical application. hence,we replaced the enzymatic hydrolyzation position ala8 with other natural amino acids. the glp-1 analogues were synthesized rapidly and efficiently under microwave irradiation,using fmoc/tbu orthogonal protection strategy. studies on blood-glucose-lowering effect of glp-1 analogues in vivo were undertaken using 10-week-old male kunming mice. the metabolic stability was tested by incubation with dipeptidyl peptidase-iv (dpp-iv). generally,xaa8-glp-1 analogues exhibit resistance to dpp-iv degradation in vitro and stronger hypoglycemic effect than glp-1. this may help to understand the structure-activity relationship of glp-1 analogues. © 2010 bentham science publishers ltd.
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کلیدواژه
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Glucagon-like peptide-1; Hypoglycemic; Microwave assisted synthesis; Solid phase peptide synthesis
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آدرس
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department of medicinal chemistry,china pharmaceutical university,24 tongjiaxiang, China, center of drug discovery,china pharmaceutical university,24 tongjiaxiang, China, center of drug discovery,china pharmaceutical university,24 tongjiaxiang, China, center of drug discovery,china pharmaceutical university,24 tongjiaxiang, China, center of drug discovery,china pharmaceutical university,24 tongjiaxiang, China, center of drug discovery,china pharmaceutical university,24 tongjiaxiang, China, department of medicinal chemistry,china pharmaceutical university,24 tongjiaxiang, China, department of math and computer,nanjing medical university,140 hanzhonglu, China, department of medicinal chemistry,china pharmaceutical university,24 tongjiaxiang, China
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Authors
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