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.
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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 |
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