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
-
The Role of Chemokines, Cytokines and Adhesion Molecules in Stem Cell Trafficking and Homing
Current Pharmaceutical Design Emerging Role for Antioxidant Therapy in Protection Against Diabetic Cardiac Complications: Experimental and Clinical Evidence for Utilization of Classic and New Antioxidants
Current Cardiology Reviews The Role of microRNA-126 in Vascular Homeostasis
Current Vascular Pharmacology Metformin in the Treatment of Polycystic Ovary Syndrome
Current Pharmaceutical Design A Review of Dietary Influences on Cardiovascular Health: Part 1: the role of Dietary Nutrients
Cardiovascular & Hematological Disorders-Drug Targets Patent Selections:
Recent Patents on Cardiovascular Drug Discovery Role of Oxidative Stress in Development of Cardiovascular Complications in Diabetes Mellitus
Current Vascular Pharmacology Nitric Oxide and its Antithrombotic Action in the Cardiovascular System
Current Drug Targets - Cardiovascular & Hematological Disorders Value of Carnitine Therapy in Kidney Dialysis Patients and Effects on Cardiac Function from Human and Animal Studies
Current Drug Targets In Silico Classification and Prediction of VIP Derivatives as VPAC1/ VPAC2 Receptor Agonists/Antagonists
Combinatorial Chemistry & High Throughput Screening Regulatory Cascade of Neuronal Loss and Glucose Metabolism
CNS & Neurological Disorders - Drug Targets Ovulation Induction in Anovulatory Patients with Polycystic Ovary Syndrome
Current Drug Therapy Nanofibers Based Tissue Engineering and Drug Delivery Approaches for Myocardial Regeneration
Current Pharmaceutical Design Diabetes and Chronic Heart Failure: From Diabetic Cardiomyopathy to Therapeutic Approach
Endocrine, Metabolic & Immune Disorders - Drug Targets Regulation of Clusterin Gene Expression
Current Protein & Peptide Science How to Advise Aspirin Use in Patients Who Need NSAIDs
Current Pharmaceutical Design Lipoproteins, Stroke and Statins
Current Vascular Pharmacology Interleukin-1 and Occlusive Arterial Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry Subject Index to Volume 4
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Why Multiples of 21? Why does Selenoprotein P Contain Multiple Selenocysteine Residues?
Current Nutraceuticals