Phage escape libraries for checkmate analysis.

Phage escape libraries for checkmate analysis. Research Abstract Details 

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Phage escape libraries for checkmate analysis. Abstract Text:

Tobin J Dickerson,Kathleen M McKenzie,Amanda S Hoyt,Malcolm R Wood,Kim D Janda,Sydney B Brenner,Richard A Lerner,

Ligand-binding epitopes of proteins can mutate rapidly, as shown by viral mutations that lead to escape from neutralizing antibodies. We have undertaken to recreate in vitro the evolutionary competition between viral mutations that allow escape from antibody binding and host mutations that generate new neutralizing antibodies to the mutated viral antigen. To examine this vital race, we describe a phage-based method that allows rapid analysis of molecules that perturb the binding of proteins to their ligands. Because the system can amplify by replication, single-molecule sensitivity can be achieved. When combinatorial protein or small-molecule libraries are studied, large numbers of binding events can be analyzed simultaneously. Such libraries may be used in a sequential phage escape format, where cycles of phage binding and release of mutants are driven by antibodies or small molecules and the difficulty of escape increases at each cycle. Ultimately, the sequencing of the viral mutants allows annotation of the allowed trajectory of escape. Likewise, sequencing of the antibody perturbants charts the chemistry of the immune system response to the viral challenge. We have termed such analysis of competing mutations a "checkmate analysis." When viral systems are studied, a checkmate analysis allows experimental evaluation of the evolutionary contest between viruses and the immune system and may predict which antibodies and small-molecule ligands should be generated in anticipation of viral mutations before these mutations create viral epidemics.

Phage escape libraries for checkmate analysis. Publishing Authors By Initials

TJ Dickerson,KM McKenzie,AS Hoyt,MR Wood,KD Janda,SB Brenner,RA Lerner,

For similar peptides: peptide library research abstracts see: peptides: peptide library research

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Phage escape libraries for checkmate analysis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 12703-8

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 23

MONTH: 07

YEAR: 2007

Phage escape libraries for checkmate analysis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Phage escape libraries for checkmate analysis. Keywords Mesh Terms:

KEYWORDS: Peptide Library

MESH TERMS: metabolism

Chemical & Substance for Abstract: Phage escape libraries for checkmate analysis. Information

Substance Name: Peptide Library

Registry Number: 0

Grant and Affiliation Information for Phage escape libraries for checkmate analysis.

AFFILIATION: Departments of Chemistry, The Skaggs Institute for Chemical Biology, and Worm Institute for Research and Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Country: United States

AGENCY: United States NIDA

GRANT: DA 018024

ACRONYM: DA

MEDLINETA: Proc Natl Acad Sci U S A

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