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PMID: 16373474 Published · ppublish English Journal Article Review

A new generation of protein display scaffolds for molecular recognition.

Protein science : a publication of the Protein Society ·Vol. 15 ·No. 1 ·2006-01-00 ·Pages 14-27

Hosse RJ, Rothe A, Power BE

Abstract

Engineered antibodies and their fragments are invaluable tools for a vast range of biotechnological and pharmaceutical applications. However, they are facing increasing competition from a new generation of protein display scaffolds, specifically selected for binding virtually any target. Some of them have already entered clinical trials. Most of these nonimmunoglobulin proteins are involved in natural binding events and have amazingly diverse origins, frameworks, and functions, including even intrinsic enzyme activity. In many respects, they are superior over antibody-derived affinity molecules and offer an ever-extending arsenal of tools for, e.g., affinity purification, protein microarray technology, bioimaging, enzyme inhibition, and potential drug delivery. As excellent supporting frameworks for the presentation of polypeptide libraries, they can be subjected to powerful in vitro or in vivo selection and evolution strategies, enabling the isolation of high-affinity binding reagents. This article reviews the generation of these novel binding reagents, describing validated and advanced alternative scaffolds as well as the most recent nonimmunoglobulin libraries. Characteristics of these protein scaffolds in terms of structural stability, tolerance to multiple substitutions, ease of expression, and subsequent applications as specific targeting molecules are discussed. Furthermore, this review shows the close linkage between these novel protein tools and the constantly developing display, selection, and evolution strategies using phage display, ribosome display, mRNA display, cell surface display, or IVC (in vitro compartmentalization). Here, we predict the important role of these novel binding reagents as a toolkit for biotechnological and biomedical applications.

MeSH Terms
Animals Combinatorial Chemistry Techniques Humans Peptide Library Protein Binding/physiology Protein Interaction Mapping Proteins/chemistry,isolation & purification,metabolism
Chemicals
Peptide Library Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hosse Ralf J
Preventative Health National Research Flagship, Parkville, Victoria 3052, Australia.
Rothe Achim
Power Barbara E
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Article Info
Journal
Protein science : a publication of the Protein Society
Abbr.
Protein Sci
ISSN
0961-8368
DOI
10.1110/ps.051817606
Published
2006-01-00
Pages
14-27
Language
English
Region
United States
NLM ID
9211750
PMCID
PMC2242358
Subset
IM
External Links
PubMed source DOI: 10.1110/ps.051817606 PMC Full Text View journal details
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