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 |
- 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
-
Insights into Targeting Colon Cancer Cell Fate at the Level of Proteoglycans / Glycosaminoglycans
Current Medicinal Chemistry The Beneficial Effects of Sulfur-containing Amino Acids on Cisplatininduced Cardiotoxicity and Neurotoxicity in Rodents
Current Medicinal Chemistry Membrane Permeable Lipophilic Cations as Mitochondrial Directing Groups
Current Topics in Medicinal Chemistry Recent Advances in Oncological Submissions of Dendrimer
Current Pharmaceutical Design A Comprehensive Review on miR-200c, A Promising Cancer Biomarker with Therapeutic Potential
Current Drug Targets Recent Development and Application of Magnetic Nanoparticles for Cell Labeling and Imaging
Mini-Reviews in Medicinal Chemistry Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and <i>in vitro</i> Studies
Current Cancer Drug Targets Role of Copper in Angiogenesis and Its Medicinal Implications
Current Medicinal Chemistry γ-Tocotrienol Induces Apoptosis in Human T Cell Lymphoma through Activation of Both Intrinsic and Extrinsic Pathways
Current Pharmaceutical Design Role of Pemetrexed and Platinums Combination in Patients with Non- Small Cell Lung Cancer
Current Drug Targets Current Targeting Strategies for Adenovirus Vectors in Cancer Gene Therapy
Current Cancer Drug Targets In-Situ Hybridization as a Molecular Tool in Cancer Diagnosis and Treatment
Current Medicinal Chemistry A Structural Insight into Hydroxamic Acid Based Histone Deacetylase Inhibitors for the Presence of Anticancer Activity
Current Medicinal Chemistry Molecular Pathology of Sarcomas
Reviews on Recent Clinical Trials Antisense Strategies
Current Molecular Medicine Clinical Development of Inhibitors of the Insulin-like Growth Factor Receptor in Oncology
Current Drug Targets Platinum Formulations as Anticancer Drugs Clinical and Pre-Clinical Studies
Current Topics in Medicinal Chemistry Recent Achievements in the Chemistry of 1,2-Diazines
Current Organic Chemistry C75, a Fatty Acid Synthase (FAS) Inhibitor
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) High Therapeutic Potential for Systemic Delivery of a Liposomeconjugated Herpes Simplex Virus
Current Cancer Drug Targets