Abstract
Cysteine (cysteinyl residue) modifications in proteins result in diversity in protein functions. The reaction specificity of a protein with a modified cysteine residue is determined by the overall conditions of the protein, including the spatial position of the cysteine residue, electrostatic interactions between cysteine residue and other charged residues, spatial interactions between the cysteine residue and a chemical compound, electrophilicity of the chemical compound, and the pH of the solution. In cysteine-dependant enzymes, each specific type of cysteine modification characterizes the catalytic mechanism of the enzyme. Recently, the catalytic mechanisms of peroxiredoxins and cysteine proteases, which contain a cysteine residue(s) in their catalytic sites, have been elucidated. In the catalytic process of peroxiredoxins, a sulfenyl intermediate is formed by oxidation of the catalytic cysteine residue. On the other hand, in cysteine proteases, the catalytic cysteine residue reacts with the carboxyl carbon of a peptide substrate to form an intermediate complex via Salkylation. In this review, we introduce the most current information on the applications of cysteine thiol chemistry for in vitro glycoprotein synthesis. Recently, a glycoprotein (monocyte chemotactic protein-3), containing an intact human complex- type sialyloligosaccharide has been chemically synthesized. The procedure used for this could have applications in the development of new protein-based drugs, including antineoplastic drugs and antibiotics. It can also potentially be applied for improving the half-life and reducing the toxicity of these drugs, and for preventing the development of multidrug resistance.
Keywords: Cysteine modification, enzyme catalysis, protein function, proteomics, redox regulation, thiol chemistry
Current Medicinal Chemistry
Title: Protein Cysteine Modifications: (2) Reactivity Specificity and Topics of Medicinal Chemistry and Protein Engineering
Volume: 16 Issue: 34
Author(s): N. Nagahara, T. Matsumura, R. Okamoto and Y. Kajihara
Affiliation:
Keywords: Cysteine modification, enzyme catalysis, protein function, proteomics, redox regulation, thiol chemistry
Abstract: Cysteine (cysteinyl residue) modifications in proteins result in diversity in protein functions. The reaction specificity of a protein with a modified cysteine residue is determined by the overall conditions of the protein, including the spatial position of the cysteine residue, electrostatic interactions between cysteine residue and other charged residues, spatial interactions between the cysteine residue and a chemical compound, electrophilicity of the chemical compound, and the pH of the solution. In cysteine-dependant enzymes, each specific type of cysteine modification characterizes the catalytic mechanism of the enzyme. Recently, the catalytic mechanisms of peroxiredoxins and cysteine proteases, which contain a cysteine residue(s) in their catalytic sites, have been elucidated. In the catalytic process of peroxiredoxins, a sulfenyl intermediate is formed by oxidation of the catalytic cysteine residue. On the other hand, in cysteine proteases, the catalytic cysteine residue reacts with the carboxyl carbon of a peptide substrate to form an intermediate complex via Salkylation. In this review, we introduce the most current information on the applications of cysteine thiol chemistry for in vitro glycoprotein synthesis. Recently, a glycoprotein (monocyte chemotactic protein-3), containing an intact human complex- type sialyloligosaccharide has been chemically synthesized. The procedure used for this could have applications in the development of new protein-based drugs, including antineoplastic drugs and antibiotics. It can also potentially be applied for improving the half-life and reducing the toxicity of these drugs, and for preventing the development of multidrug resistance.
Export Options
About this article
Cite this article as:
Nagahara N., Matsumura T., Okamoto R. and Kajihara Y., Protein Cysteine Modifications: (2) Reactivity Specificity and Topics of Medicinal Chemistry and Protein Engineering, Current Medicinal Chemistry 2009; 16 (34) . https://dx.doi.org/10.2174/092986709789760643
DOI https://dx.doi.org/10.2174/092986709789760643 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Apoptosis Caused by Triterpenes and Phytosterols and Antioxidant Activity of an Enriched Flavonoid Extract from Passiflora mucronata
Anti-Cancer Agents in Medicinal Chemistry Post-Transcriptional and Post-translational Regulation of Central Carbon Metabolic Enzymes in Cancer
Anti-Cancer Agents in Medicinal Chemistry Application of Resveratrol in Diabetes: Rationale, Strategies and Challenges
Current Molecular Medicine Outcome Measures Following Sonodynamic Photodynamic Therapy – A Case Series
Current Drug Therapy Gene Therapy Approaches for the Selective Killing of Cancer Cells
Current Pharmaceutical Design Monitoring of Environmental Metals in Human Blood: The Need for Data Validation
Current Analytical Chemistry Profiling of Enzymatic Activities Using Peptide Arrays
Mini-Reviews in Organic Chemistry Separation of Ginseng Active Ingredients and their Roles in Cancer Metastasis Supplementary Therapy
Current Drug Metabolism Radiolabeled Imaging Probes Targeting Angiogenesis for Personalized Medicine
Current Pharmaceutical Design OX40 and OX40L Interaction in Cancer
Current Medicinal Chemistry Development of <sup>18</sup>F-Labeled PET Probes for Imaging Cell Proliferation
Current Topics in Medicinal Chemistry Role of Netrin-1 Beyond the Brain: From Biomarker of Tissue Injury to Therapy for Inflammatory Diseases
Recent Patents on Biomarkers Blending of Polyethylenimine with a Cationic Polyurethane Greatly Enhances Both DNA Delivery Efficacy and Reduces the Overall Cytotoxicity
Current Pharmaceutical Biotechnology V. Amygdalina: Folk Medicine, Analysis, and Potential Application for Cancer Treatment
Current Pharmaceutical Analysis Inhibition of Early Biochemical Defects in Prodromal Huntington’s disease by Simultaneous Activation of Nrf2 and Elevation of Multiple Micronutrients
Current Aging Science Thymoquinone: Major Molecular Targets, Prominent Pharmacological Actions and Drug Delivery Concerns
Current Bioactive Compounds Morpho-Functional Features of In-Vitro Cell Death Induced by Physical Agents
Current Pharmaceutical Design Prostate Cancer, miRNAs, Metallothioneins and Resistance to Cytostatic Drugs
Current Medicinal Chemistry Indoor Dust Levels of Perfluoroalkyl Substances (PFASs) and the Role of Ingestion as an Exposure Pathway: A Review
Current Organic Chemistry Crosstalk of Long Non-coding RNAs and EMT: Searching the Missing Pieces of an Incomplete Puzzle for Lung Cancer Therapy
Current Cancer Drug Targets