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
-
Reperfusion Therapies for Acute Ischemic Stroke: An Update
Current Cardiology Reviews The Effect of a Common Antibiotics Doxycycline on Non-Healing Chronic Wound
Current Pharmaceutical Biotechnology Research and Clinical Applications of Optical Coherence Tomography in Invasive Cardiology: A Review
Current Cardiology Reviews Retinoids: Pleiotropic Agents of Therapy for Vascular Diseases?
Current Drug Targets - Cardiovascular & Hematological Disorders Systemic Lupus Erythematosus-Related Interstitial Lung Disease
Current Rheumatology Reviews Gene Therapy as a Novel Pharmaceutical Intervention for Stroke
Current Pharmaceutical Design Insight to the Pathophysiology of Stable Angina Pectoris
Current Pharmaceutical Design Will Pharmacogenetics Predict Response to Therapies in Rheumatoid Arthritis?
Current Pharmacogenomics Metabolic Control of Glia-Mediated Neuroinflammation
Current Alzheimer Research Gene-Activation Mechanisms in the Regression of Atherosclerosis, Elimination of Diabetes Type 2, and Prevention of Dementia
Current Molecular Medicine Heart Failure in South America
Current Cardiology Reviews Recent Advances on the Antiatherogenic Effects of HDL-Derived Proteins and Mimetic Peptides
Current Pharmaceutical Design Editorial [Hot Topic: Drugs Targeted to Improve Endothelial Function: Clinical Correlates Between Sexual and Internal Medicine (Executive Editor: Antonio Aversa)]
Current Pharmaceutical Design Apathy: A Conceptual Review
Current Psychiatry Research and Reviews Long-Term Metabolic Consequences in Patients with a History of Gestational Diabetes
Current Pharmaceutical Design Extraction of Triacylglycerols and Fatty Acids Using Supercritical Fluids - Review
Current Analytical Chemistry Pharmacotherapy Before and After Endovascular Repair of Abdominal Aortic Aneurysms
Current Vascular Pharmacology Neutrophil Derived Microvesicles: Emerging Role of a Key Mediator to the Immune Response
Endocrine, Metabolic & Immune Disorders - Drug Targets Use of Alternative Antiplatelet Agents for Clopidogrel Hypersensitivity
Current Vascular Pharmacology Interstitial Lung Disease in Idiopathic Inflammatory Myopathy
Current Rheumatology Reviews