Abstract
Proteases are potential or realized therapeutic targets in a wide variety of pathological conditions. Moreover, proteases are classical subjects for studies of enzymatic and regulatory mechanisms. We here review the literature on nucleic acid aptamers selected with proteases as targets. Designing small molecule protease inhibitors of sufficient specificity has proved a daunting task. Aptamers seem to represent a promising alternative. In our review, we concentrate on biochemical mechanisms of aptamer selection, proteinaptamer recognition, protease inhibition, and advantages of aptamers for pharmacological intervention with pathophysiological functions of proteases. Aptamers can be selected so that they bind their targets highly specifically and with affinities corresponding to KD values in the nM range. Aptamers can be selected so that they recognize their targets conformation-specifically, for instance with vastly different affinities to zymogen and active enzyme forms. Furthermore, aptamers can be selected to inhibit the enzyme activity of the target proteases, but also to inhibit functionally important exosite interactions, for instance cofactor binding. Several protease-inhibiting aptamers, directed against blood coagulation factors, are in clinical trials as anticoagulant drugs. Several of the studies on protease-binding aptamers have been pioneering and trend-setting in the field. The work with protease-binding aptamers also demonstrates many interesting examples of non-standard selection strategies and of new principles for regulating the activity of the inhibitory action of aptamers of general interest to researchers working with nucleic acid aptamers.
Keywords: Cancer, coagulation, exosite, extracellular matrix, protease aptamer, review, SELEX, thrombin
Current Medicinal Chemistry
Title: Nucleic Acid Aptamers Against Proteases
Volume: 18 Issue: 27
Author(s): D. M. Dupont, L. M. Andersen, K. A. Botkjaer and P. A. Andreasen
Affiliation:
Keywords: Cancer, coagulation, exosite, extracellular matrix, protease aptamer, review, SELEX, thrombin
Abstract: Proteases are potential or realized therapeutic targets in a wide variety of pathological conditions. Moreover, proteases are classical subjects for studies of enzymatic and regulatory mechanisms. We here review the literature on nucleic acid aptamers selected with proteases as targets. Designing small molecule protease inhibitors of sufficient specificity has proved a daunting task. Aptamers seem to represent a promising alternative. In our review, we concentrate on biochemical mechanisms of aptamer selection, proteinaptamer recognition, protease inhibition, and advantages of aptamers for pharmacological intervention with pathophysiological functions of proteases. Aptamers can be selected so that they bind their targets highly specifically and with affinities corresponding to KD values in the nM range. Aptamers can be selected so that they recognize their targets conformation-specifically, for instance with vastly different affinities to zymogen and active enzyme forms. Furthermore, aptamers can be selected to inhibit the enzyme activity of the target proteases, but also to inhibit functionally important exosite interactions, for instance cofactor binding. Several protease-inhibiting aptamers, directed against blood coagulation factors, are in clinical trials as anticoagulant drugs. Several of the studies on protease-binding aptamers have been pioneering and trend-setting in the field. The work with protease-binding aptamers also demonstrates many interesting examples of non-standard selection strategies and of new principles for regulating the activity of the inhibitory action of aptamers of general interest to researchers working with nucleic acid aptamers.
Export Options
About this article
Cite this article as:
M. Dupont D., M. Andersen L., A. Botkjaer K. and A. Andreasen P., Nucleic Acid Aptamers Against Proteases, Current Medicinal Chemistry 2011; 18 (27) . https://dx.doi.org/10.2174/092986711797189556
DOI https://dx.doi.org/10.2174/092986711797189556 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- 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
- Announcements
Related Articles
-
Selective Serotonin-norepinephrine Re-uptake Inhibition Limits Renovas-cular-hypertension Induced Cognitive Impairment, Endothelial Dysfunction, and Oxidative Stress Injury
Current Neurovascular Research Intestinal Barrier Dysfunction Participates in the Pathophysiology of Ischemic Stroke
CNS & Neurological Disorders - Drug Targets An Overview of Bioactive Peptides for in vivo Imaging and Therapy in Human Diseases
Mini-Reviews in Medicinal Chemistry Directing Cardiomyogenic Differentiation and Transdifferentiation By Ectopic Gene Expression – Direct Transition Or Reprogramming Detour?
Current Gene Therapy Investigation of In Vitro Antiurolithic Property of Purified Polyphenols from Selected Medicinal Plants to Inhibit Renal Calculi
Current Traditional Medicine Transcranial Doppler Ultrasonography: Current Status
Current Medical Imaging A Review of the Chemical and Pharmacological Aspects of the Genus Marrubium
Current Pharmaceutical Design Mitochondrial Targeting for Development of Novel Drug Strategies in Brain Injury
Central Nervous System Agents in Medicinal Chemistry Hematopoietic Colony Stimulating Factors in Cardiovascular and Pulmonary Remodeling: Promoters or Inhibitors?
Current Pharmaceutical Design G Protein Coupled Receptors - In Silico Drug Discovery and Design
Current Topics in Medicinal Chemistry Modulation of Renal Tubular Cell Survival: Where is the Evidence?
Current Medicinal Chemistry Oxidative Stress and the Use of Antioxidants for the Treatment of Rheumatoid Arthritis
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Editorial: Still Water Runs Deep
Current Molecular Medicine Mechanisms of Neurodegeration in Type 2 Diabetes and the Neuroprotective Potential of Dipeptidyl Peptidase 4 Inhibitors
Current Medicinal Chemistry Metabolomics and the Diagnosis of Human Diseases -A Guide to the Markers and Pathophysiological Pathways Affected
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Chemical Biology Hyperthermia: From Diagnostic and Treatments to New Discoveries
Recent Patents on Biotechnology Kinins as Therapeutic Agents in Cardiovascular and Renal Diseases
Current Pharmaceutical Design Inwardly Rectifying Potassium Channels in the Regulation of Vascular Tone
Current Drug Targets The Roles of β-Carotene in Cardiomyocytes
Current Nutrition & Food Science