Abstract
The RGD sequence was used to design potent hirudin isoform 3 mimetic peptides with both antithrombin activity and antiplatelet aggregation activity. The RGD and proline were inserted between the catalytic active binding domain (D-Phe-Pro-Arg-Pro) on the N-terminus and the anion-binding exosite binding domain (QGDFEPIPEDAYDE) on the Cterminus. Thrombin titration assay and ATP-induced platelet aggregation test revealed that the peptide with the linker RGDWP or RGDGP possessed potent antithrombin and antiplatelet activities, while other peptides without the Pro residue in the linker only showed antithrombin activity. Similar results were obtained in the RGD-containing hirulog-1 variants. Our study indicates that the inserted Pro residue facilitates the exposure of RGD and the binding of the peptide to glycoprotein IIb/IIIa (GPIIb/IIIa). The strategy of combining the RGD sequence and the Pro residue may be used for future designs of bifunctional antithrombotic agents.
Keywords: Antiplatelet aggregation, antithrombin, hirudin, mimetic peptide, RGD-motif, .
Protein & Peptide Letters
Title:Construction and Characterization of Novel Hirulog Variants with Antithrombin and Antiplatelet Activities
Volume: 21 Issue: 1
Author(s): Zheng Yu, Yuanyuan Huang, Yu Wang, Chen Dai, Mingxin Dong, Zhuguo Liu, Shuo Yu, Jie Hu and Qiuyun Dai
Affiliation:
Keywords: Antiplatelet aggregation, antithrombin, hirudin, mimetic peptide, RGD-motif, .
Abstract: The RGD sequence was used to design potent hirudin isoform 3 mimetic peptides with both antithrombin activity and antiplatelet aggregation activity. The RGD and proline were inserted between the catalytic active binding domain (D-Phe-Pro-Arg-Pro) on the N-terminus and the anion-binding exosite binding domain (QGDFEPIPEDAYDE) on the Cterminus. Thrombin titration assay and ATP-induced platelet aggregation test revealed that the peptide with the linker RGDWP or RGDGP possessed potent antithrombin and antiplatelet activities, while other peptides without the Pro residue in the linker only showed antithrombin activity. Similar results were obtained in the RGD-containing hirulog-1 variants. Our study indicates that the inserted Pro residue facilitates the exposure of RGD and the binding of the peptide to glycoprotein IIb/IIIa (GPIIb/IIIa). The strategy of combining the RGD sequence and the Pro residue may be used for future designs of bifunctional antithrombotic agents.
Export Options
About this article
Cite this article as:
Yu Zheng, Huang Yuanyuan, Wang Yu, Dai Chen, Dong Mingxin, Liu Zhuguo, Yu Shuo, Hu Jie and Dai Qiuyun, Construction and Characterization of Novel Hirulog Variants with Antithrombin and Antiplatelet Activities, Protein & Peptide Letters 2014; 21 (1) . https://dx.doi.org/10.2174/092986652101131219111458
DOI https://dx.doi.org/10.2174/092986652101131219111458 |
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
-
Pathophysiology of Idiopathic Atrial Fibrillation - Prognostic and Treatment Implications
Current Pharmaceutical Design Dyslipidemia and Cardiovascular Disease Prevention in South Asians: A Review and Discussion of Causes, Challenges and Management Strategies
Current Diabetes Reviews Dietary Transition in the South Asian Diaspora: Implications for Diabetes Prevention Strategies
Current Diabetes Reviews The Heat Stress Response and Diabetes: More Room for Mitochondrial Implication
Current Pharmaceutical Design Twin-to-Twin Transfusion Syndrome: From Placental Anastomoses to Long-Term Neurodevelopmental Outcome
Current Pediatric Reviews MicroRNAs as Biomarkers for Birth Defects
MicroRNA HIV-Induced Abnormalities in Myelopoiesis and their Recovery Following Antiretroviral Therapy
Current HIV Research Prevention and treatment of atherosclerosis with flaxseed -derived compound secoisolariciresinol diglucoside
Current Pharmaceutical Design Plant Sterols and Stanols in the Treatment of Dyslipidemia: New Insights into Targets and Mechanisms Related to Cardiovascular Risk
Current Pharmaceutical Design Targeting Antioxidants to Mitochondria: A Potential New Therapeutic Strategy for Cardiovascular Diseases
Current Pharmaceutical Design Neuroinflammatory Markers in Spontaneously Hypertensive Rat Brain: An Immunohistochemical Study
CNS & Neurological Disorders - Drug Targets Genetic Variation and Atherosclerosis
Current Genomics The Use of Gene Therapy Tools in Reproductive Immunology Research
Current Gene Therapy Pharmacological Treatment of Obesity, Food Intake, and Reversal of Metabolic Disorders
Current Nutrition & Food Science Phenomics of Vascular Disease: The Systematic Approach to the Combination Therapy
Current Vascular Pharmacology Smoking and Hypertension: Independent or Additive Effects to Determining Vascular Damage?
Current Vascular Pharmacology A Review on Rheumatoid Arthritis Interventions and Current Developments
Current Drug Targets RAGE Signaling in Cell Adhesion and Inflammation
Current Pediatric Reviews Myocardial Infarction after Rituximab Treatment for Rheumatoid Arthritis: Is there a Link?
Current Pharmaceutical Design Myocardial Energy Substrate Metabolism in Heart Failure : from Pathways to Therapeutic Targets
Current Pharmaceutical Design