Abstract
This review describes the design process from conception through realisation and optimisation of a minibody - a minimised antibody. The result was a proteinaceous molecule of novel fold and metal binding activity. We explain how combinatorial approaches, using phage display libraries, were used to randomise loop regions of the minibody. Variants were then selected for desired activities including in vitro inhibition of human interleukin-6 and the protease of the non-structural protein, NS3, of the hepatitis C virus. One such variant was successfully minimised further to produce a cyclic peptide with similar inhibition properties. Thus the work reviewed provides examples of two important processes in protein design and protein minimisation. We conclude by discussing the role of such studies in medical applications and small molecule drug discovery. We also highlight the potential of our work and similar techniques in the post-genomic era.
Keywords: human interleukin-6, protease, hepatitis c virus, ns3 protease, camelised domains, peptide inhibitor
Combinatorial Chemistry & High Throughput Screening
Title: Of Minibody, Camel and Bacteriophage
Volume: 4 Issue: 5
Author(s): C. K. Vaughan and M. Sollazzo
Affiliation:
Keywords: human interleukin-6, protease, hepatitis c virus, ns3 protease, camelised domains, peptide inhibitor
Abstract: This review describes the design process from conception through realisation and optimisation of a minibody - a minimised antibody. The result was a proteinaceous molecule of novel fold and metal binding activity. We explain how combinatorial approaches, using phage display libraries, were used to randomise loop regions of the minibody. Variants were then selected for desired activities including in vitro inhibition of human interleukin-6 and the protease of the non-structural protein, NS3, of the hepatitis C virus. One such variant was successfully minimised further to produce a cyclic peptide with similar inhibition properties. Thus the work reviewed provides examples of two important processes in protein design and protein minimisation. We conclude by discussing the role of such studies in medical applications and small molecule drug discovery. We also highlight the potential of our work and similar techniques in the post-genomic era.
Export Options
About this article
Cite this article as:
Vaughan K. C. and Sollazzo M., Of Minibody, Camel and Bacteriophage, Combinatorial Chemistry & High Throughput Screening 2001; 4 (5) . https://dx.doi.org/10.2174/1386207013330986
DOI https://dx.doi.org/10.2174/1386207013330986 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Advances in the design of antibody & protein with conformational dynamics and artificial intelligence approaches
“Antibodies & Protein Design” section focuses on the utilization of multiple strategies to engineer and optimize antibodies and proteins that serve diverse analytical strategies, such as combinatorial protein design, structure-based design, sequence-based design, and other techniques that incorporate principles of protein-protein interactions, allosteric regulation, and post-translational modifications. Example applications include ...read more
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute-force experimentation, which can be time-consuming and resource-intensive. Spectral graph theory, a branch of mathematics dealing with the properties of graphs in relation to the eigenvalues and eigenvectors of matrices associated ...read more
Intersection of Chemical Graph Theory and Molecular Sciences
Chemical graph theory has become increasingly critical in molecular sciences, offering advanced capabilities in the modeling, design, and analysis of chemical structures via molecular graphs. This special issue aims to not only explore these fundamental aspects but also to push the boundaries of CCHTS applications. By integrating the concept of ...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
-
The Etiology of Hypertension in the Metabolic Syndrome Part One: An Introduction to the History, the Concept and the Models
Current Vascular Pharmacology The Role of Novel Biomarkers of Cardiovascular Disease in Chronic Kidney Disease: Focus on Adiponectin and Leptin
Current Cardiology Reviews Point-of-Care Genetic Tests for Infectious Disease: Legal Considerations
Current Pharmacogenomics and Personalized Medicine Mitochondrial Pathology in Osteoarthritic Chondrocytes
Current Drug Targets Remodeling of the Myocardium and Potential Targets in the Collagen Degradation and Synthesis Pathways
Current Drug Targets - Cardiovascular & Hematological Disorders Correlation Between White Blood Cell Count and Insulin Resistance in Type 2 Diabetes
Current Diabetes Reviews Therapeutic Challenges in Neuroendocrine Tumors
Anti-Cancer Agents in Medicinal Chemistry The Modulatory Effect of Lead Drug Candidates on Inflammatory Gene Expression in Sepsis: A Mini-Review
Current Drug Discovery Technologies Targeting Epigenome As An Innovative Pharmacological Strategy For Castration-resistant Prostate Cancer
Clinical Cancer Drugs Targeting Role of Glioma Stem Cells for Glioblastoma Multiforme
Current Medicinal Chemistry A Proteomics Perspective: From Animal Welfare to Food Safety
Current Protein & Peptide Science Regulation of Blood Flow by Prostaglandins
Current Vascular Pharmacology Membrane Interactive α-Helices in GPCRs as a Novel Drug Target
Current Protein & Peptide Science Epidemiology and Risk Factors for Severe Delayed Drug Hypersensitivity Reactions
Current Pharmaceutical Design A Novel Recombinant Modified Vaccinia Ankara Virus expressing Interleukin-13 Receptor α2 Antigen for Potential Cancer Immunotherapy
Current Molecular Medicine Genetically-modified Stem Cell in Regenerative Medicine and Cancer Therapy; A New Era
Current Gene Therapy siRNA Modifications and Sub-Cellular Localization: A Question of Intracellular Transport?
Current Pharmaceutical Design NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase: Structure and Biological Functions
Current Pharmaceutical Design Therapeutic Boosting of the Immune Response: Turning to CD14 for Help
Current Pharmaceutical Biotechnology Genetic Markers of the Host to Predict the Efficacy of Colorectal Cancer Targeted Therapy
Current Medicinal Chemistry