Abstract
Structural changes of human serum albumin (HSA) caused by old age and coexisting diseases result in differences in the binding of doxazosin (DOX). DOX is a postsynaptic α1- adrenoreceptor antagonist used for treatment of hypertension and benign prostatic hyperplasia. In elderly people suffering from various renal or hepatic diseases the significant portion of N-form of human serum albumin (normal) is converted to A-form (aged). The differences in binding of doxazosin to N- and Aform of albumin are an important factor, which may determines therapeutic dosage and toxicity of the test drug. To indicate these differences, the technique of fluorescence spectroscopy was used. The association constant (Ka) obtained from fluorescence quenching demonstrated that doxazosin has higher affinity for AHSA than for HSA. In order to describe the cooperativity in binding process, the values of the Hill’s coefficient has been analysed. For DOX-HSA system (λex 295 nm) Hill’s coefficient is close to 1 and it indicates that there is a single class of binding sites. For DOX-HSA (λex 275 nm) and DOX-AHSA (λex 275 nm and λex 295 nm) systems we observed positive cooperativity (nH>1). A greater red shift of fluorescence emission maximum of AHSA than HSA in the presence of DOX was observed. This suggests that the binding of DOX to AHSA was accompanied by a stronger increase in polarity around the fluorophores in comparison to HSA. The binding interaction between DOX and HSA has been also studied by molecular docking simulation.
Keywords: N-A transition, molecular aging, human serum albumin, doxazosin.
Current Protein & Peptide Science
Title:Analysis of Aged Human Serum Albumin Affinity for Doxazosin
Volume: 17 Issue: 2
Author(s): Mariola Chudzik, Joanna Równicka – Zubik, Jadwiga Pożycka, Bartosz Pawelczak and Anna Sulkowska
Affiliation:
Keywords: N-A transition, molecular aging, human serum albumin, doxazosin.
Abstract: Structural changes of human serum albumin (HSA) caused by old age and coexisting diseases result in differences in the binding of doxazosin (DOX). DOX is a postsynaptic α1- adrenoreceptor antagonist used for treatment of hypertension and benign prostatic hyperplasia. In elderly people suffering from various renal or hepatic diseases the significant portion of N-form of human serum albumin (normal) is converted to A-form (aged). The differences in binding of doxazosin to N- and Aform of albumin are an important factor, which may determines therapeutic dosage and toxicity of the test drug. To indicate these differences, the technique of fluorescence spectroscopy was used. The association constant (Ka) obtained from fluorescence quenching demonstrated that doxazosin has higher affinity for AHSA than for HSA. In order to describe the cooperativity in binding process, the values of the Hill’s coefficient has been analysed. For DOX-HSA system (λex 295 nm) Hill’s coefficient is close to 1 and it indicates that there is a single class of binding sites. For DOX-HSA (λex 275 nm) and DOX-AHSA (λex 275 nm and λex 295 nm) systems we observed positive cooperativity (nH>1). A greater red shift of fluorescence emission maximum of AHSA than HSA in the presence of DOX was observed. This suggests that the binding of DOX to AHSA was accompanied by a stronger increase in polarity around the fluorophores in comparison to HSA. The binding interaction between DOX and HSA has been also studied by molecular docking simulation.
Export Options
About this article
Cite this article as:
Chudzik Mariola, Równicka – Zubik Joanna, Pożycka Jadwiga, Pawelczak Bartosz and Sulkowska Anna, Analysis of Aged Human Serum Albumin Affinity for Doxazosin, Current Protein & Peptide Science 2016; 17 (2) . https://dx.doi.org/10.2174/1389203716666151102103923
DOI https://dx.doi.org/10.2174/1389203716666151102103923 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
-
Vasoactive Renal Factors and the Progression of Diabetic Nephropathy
Current Pharmaceutical Design Comparison of Status Epilepticus Models Induced by Pilocarpine and Nerve Agents - A Systematic Review of the Underlying Aetiology and Adopted Therapeutic Approaches
Current Medicinal Chemistry Differential Action of Phytochemicals on Platelet Apoptosis: A Biological Overview
Current Medicinal Chemistry The Significance of Oxidized Low-Density Lipoprotein in Body Fluids as a Marker Related to Diseased Conditions
Current Medicinal Chemistry Antioxidants in Peripheral Arterial Disease
Current Drug Targets - Cardiovascular & Hematological Disorders Urocortins: Take Them to Heart
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Repurposing of Existing Drugs for the Bacterial Infections: An In silico and In vitro Study
Infectious Disorders - Drug Targets Therapeutic Approaches for Reducing C-Reactive Protein (CRP) Levels and the Associated Cardiovascular Risk
Current Chemical Biology The Pattern of Abbreviation Use in Prescriptions: A Way Forward in Eliminating Error-Prone Abbreviations and Standardisation of Prescriptions
Current Drug Safety Simultaneous Monitoring of Febuxostat and Uric Acid in Human Serum Samples Using the Direct Square-Wave Voltammetric Method
Current Analytical Chemistry The Role Played by Serine Proteases in the Development and Worsening of Vascular Complications in Type 1 Diabetes Mellitus
Current Diabetes Reviews Site-related Effects of Relaxin in the Gastrointestinal Tract Through Nitric Oxide Signalling: An Updated Report
Current Protein & Peptide Science Leptin as Clinical Target
Recent Patents on Inflammation & Allergy Drug Discovery Gallic Acid Attenuates Oleic Acid-induced Proliferation of Vascular Smooth Muscle Cell Through Regulation of AMPK-eNOS-FAS Signaling
Current Medicinal Chemistry Noradrenaline-mediated Inhibition of Inflammatory Cytokines is Altered in Macrophages from Obese Zucker Rats: Effect of Habitual Exercise
Endocrine, Metabolic & Immune Disorders - Drug Targets Medicinal Chemistry of Antimigraine Drugs
Current Medicinal Chemistry Hydrogen Sulfide Regulates Vascular Inflammation and its Related Signaling Pathways
Current Signal Transduction Therapy Association Serum S100B Protein in Alzheimer’s Disease: A Case Control Study from South India
Current Alzheimer Research Subclinical Vitamin B12 Deficiency and Heart Rate Variability Across Life Cycle
Current Aging Science Oleic Acid Vesicles for Transdermal Delivery of Propranolol Hydrochloride: Development and Characterization
Current Drug Therapy