Abstract
The cytotoxic properties of naturally occurring or engineered RNases correlate well with their efficiency of cellular internalization and digestion level of cellular RNA. Cationized RNases are considered to adsorb to the anionic cellular surface by Coulombic interactions, and then become efficiently internalized into cells by an endocytosis-like pathway. The design of cytotoxic RNases by chemical modification of surface carboxylic residues is one of the powerful strategies for enhancing cellular internalization and is accompanied with a decreased sensitivity for the cytoplasmic RNase inhibitor. Although chemically modified cationized RNases showed decreased ribonucleolytic activity, improved endocytosis and decreased affinity to the endogenous RNase inhibitor conclusively contribute to their ability to digest cellular RNA. Furthermore, the cytotoxicity of cationized RNases can be drastically enhanced by co-endocytosis with an endosomedestabilizing peptide. Since efficient cellular internalization of proteins into living cells is an important technology for biotechnology, studies concerning the design of cytotoxic RNases provided general perceptions for protein-based drug design.
Keywords: Chemical conjugation, polyethylenimine, protein transduction, endocytosis, cytotoxic Rnase
Current Pharmaceutical Biotechnology
Title: Design of Cytotoxic Ribonucleases by Cationization to Enhance Intracellular Protein Delivery
Volume: 9 Issue: 3
Author(s): Junichiro Futami and Hidenori Yamada
Affiliation:
Keywords: Chemical conjugation, polyethylenimine, protein transduction, endocytosis, cytotoxic Rnase
Abstract: The cytotoxic properties of naturally occurring or engineered RNases correlate well with their efficiency of cellular internalization and digestion level of cellular RNA. Cationized RNases are considered to adsorb to the anionic cellular surface by Coulombic interactions, and then become efficiently internalized into cells by an endocytosis-like pathway. The design of cytotoxic RNases by chemical modification of surface carboxylic residues is one of the powerful strategies for enhancing cellular internalization and is accompanied with a decreased sensitivity for the cytoplasmic RNase inhibitor. Although chemically modified cationized RNases showed decreased ribonucleolytic activity, improved endocytosis and decreased affinity to the endogenous RNase inhibitor conclusively contribute to their ability to digest cellular RNA. Furthermore, the cytotoxicity of cationized RNases can be drastically enhanced by co-endocytosis with an endosomedestabilizing peptide. Since efficient cellular internalization of proteins into living cells is an important technology for biotechnology, studies concerning the design of cytotoxic RNases provided general perceptions for protein-based drug design.
Export Options
About this article
Cite this article as:
Futami Junichiro and Yamada Hidenori, Design of Cytotoxic Ribonucleases by Cationization to Enhance Intracellular Protein Delivery, Current Pharmaceutical Biotechnology 2008; 9 (3) . https://dx.doi.org/10.2174/138920108784567326
DOI https://dx.doi.org/10.2174/138920108784567326 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...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
Related Articles
-
Organoselenium Compounds in Cancer Chemoprevention
Mini-Reviews in Medicinal Chemistry Stem Cell-Derived Microvesicles: A Cell Free Therapy Approach to the Regenerative Medicine
Current Biotechnology Circulating Tumor Cells (CTCs) as a Liquid Biopsy Material and Drug Target
Current Drug Targets Genistein Potentiates the Anti-cancer Effects of Gemcitabine in Human Osteosarcoma via the Downregulation of Akt and Nuclear Factor-κB Pathway
Anti-Cancer Agents in Medicinal Chemistry Cancer Targeted Therapy Strategy: The Pathologist’s Perspectives
Current Cancer Drug Targets Therapeutic Value of Black Seed Oil in Methotrexate Hepatotoxicity in Egyptian Children with Acute Lymphoblastic Leukemia
Infectious Disorders - Drug Targets Platinum Formulations as Anticancer Drugs Clinical and Pre-Clinical Studies
Current Topics in Medicinal Chemistry MicroRNAs as Diagnostic, Prognostic and Predictive Biomarkers of Ovarian Cancer
Recent Patents on Biomarkers Cyclotron Production of PET Radiometals in Liquid Targets: Aspects and Prospects
Current Radiopharmaceuticals The Rational Design of Anticancer Platinum Complexes: The Importance of the Structure-Activity Relationship
Current Medicinal Chemistry Lactate Transporters and pH Regulation: Potential Therapeutic Targets in Glioblastomas
Current Cancer Drug Targets Exploring the Mitochondrial Apoptotic Cell Death Landscape and Associated Components Serving as Molecular Targets, Primarily for Synthetic and Natural Drugs Targeting Oncology Therapeutics
Current Molecular Pharmacology The Role of Pemetrexed Combined with Targeted Agents for Non-Small Cell Lung Cancer
Current Drug Targets Biopolymer-based Scaffolds for Tissue Engineering Applications
Current Drug Targets Predicting Targeted Polypharmacology for Drug Repositioning and Multi- Target Drug Discovery
Current Medicinal Chemistry Lipid-Based Vectors for Therapeutic mRNA-Based Anti-Cancer Vaccines
Current Pharmaceutical Design Protectors of the Mitochondrial Permeability Transition Pore Activated by Iron and Doxorubicin
Current Cancer Drug Targets HtrA Serine Proteases as Potential Therapeutic Targets in Cancer
Current Cancer Drug Targets Is Src a Viable Target for Treating Solid Tumours?
Current Cancer Drug Targets Novel Drug-Induced Pulmonary Complications in Cancer Patients You Can Save Life!
Current Respiratory Medicine Reviews