Abstract
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.
Keywords: Glucagon-like peptide-1, microwave assisted synthesis, solid phase peptide synthesis, hypoglycemic
Protein & Peptide Letters
Title: Synthesis and Bioactivity Evaluation of Dipeptidyl Peptidase IV Resistant Glucagon-like Peptide-1 Analogues
Volume: 17 Issue: 10
Author(s): Jinpei Zhou, Shuaijian Ni, Huibin Zhang, Hai Qian, Yushi Chi, Wenlong Huang, Lu Yu, Xiaowen Hu and Wei Chen
Affiliation:
Keywords: Glucagon-like peptide-1, microwave assisted synthesis, solid phase peptide synthesis, hypoglycemic
Abstract: 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.
Export Options
About this article
Cite this article as:
Zhou Jinpei, Ni Shuaijian, Zhang Huibin, Qian Hai, Chi Yushi, Huang Wenlong, Yu Lu, Hu Xiaowen and Chen Wei, Synthesis and Bioactivity Evaluation of Dipeptidyl Peptidase IV Resistant Glucagon-like Peptide-1 Analogues, Protein & Peptide Letters 2010; 17 (10) . https://dx.doi.org/10.2174/092986610792231546
DOI https://dx.doi.org/10.2174/092986610792231546 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery Pharmacological Treatments for Obesity-Related Hypertension
Current Hypertension Reviews Alstrom Syndrome: Genetics and Clinical Overview
Current Genomics Poly (ADP-Ribose) Polymerase-1 (PARP-1) as Immune Regulator
Endocrine, Metabolic & Immune Disorders - Drug Targets Breastfeeding Policy Development and the Prevention of Obesity
Current Pediatric Reviews SGLT2 Inhibitors and Cardiovascular Outcomes: Do They Differ or There is a Class Effect? New Insights from the EMPA-REG OUTCOME trial and the CVD-REAL Study
Current Cardiology Reviews Adult Stem Cells and the Clinical Arena: Are we Able to Widely Use this Therapy in Patients with Chronic Limbs Arteriopathy and Ischemic Ulcers without Possibility of Revascularization?
Cardiovascular & Hematological Agents in Medicinal Chemistry Hypertension Impairs Cerebral Blood Flow in a Mouse Model for Alzheimer’s Disease
Current Alzheimer Research Effect of Fasting Ramadan in Diabetes Control Status - Application of Extensive Diabetes Education, Serum Creatinine with HbA1c Statistical ANOVA and Regression Models to Prevent Hypoglycemia
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Circulating Levels of Uric Acid and Risk for Metabolic Syndrome
Current Diabetes Reviews Seeds of Mung Bean (<i>Vigna radiata</i> (L.) R.Wilczek): Taxonomy, Phytochemistry, Medicinal Uses and Pharmacology
Current Bioactive Compounds Oxidative Stress and Inflammation: Their Role in the Pathogenesis of Peripheral Artery Disease with or Without Type 2 Diabetes Mellitus
Current Vascular Pharmacology Plasminogen Activator Inhibitor-1 and Restenosis
Current Drug Targets Uncontrolled Hypertension and Oncology: Clinical Tips
Current Vascular Pharmacology Interaction between Thienopyridines and Proton Pump Inhibitors
Cardiovascular & Hematological Disorders-Drug Targets Chemokine Contribution in Stem Cell Engraftment into the Infarcted Myocardium
Current Stem Cell Research & Therapy The Forkhead Transcription Factor FOXO3a Controls Microglial Inflammatory Activation and Eventual Apoptotic Injury through Caspase 3
Current Neurovascular Research Kinetic Measurement Techniques in the Evaluation of Lipid Metabolism
Current Drug Discovery Technologies Critical Illness in Obstetric Patients: Introduction and Epidemiology
Current Women`s Health Reviews Health Benefits of Honey: Implications for Treating Cardiovascular Diseases
Current Nutrition & Food Science