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Miniature Protein Inhibitors of the p53–hDM2 Interaction
Author(s) -
Kritzer Joshua A.,
Zutshi Reena,
Cheah Mingtatt,
Ran F. Ann,
Webman Rachel,
Wongjirad Taritree M.,
Schepartz Alanna
Publication year - 2006
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200500324
Subject(s) - epitope , scaffold protein , protein engineering , scaffold , microbiology and biotechnology , protein design , target protein , p53 protein , computational biology , chemistry , biochemistry , protein structure , biology , antibody , enzyme , computer science , genetics , signal transduction , apoptosis , gene , database
Small but perfectly formed . A library of miniature protein variants was constructed that presented the minimal recognition epitope of the human double‐minute 2 oncoprotein (hDM2), which was derived from the activation domain of p53 (p53AD). This library was optimized (see scheme) to yield several miniature proteins with robust folds and nanomolar affinity for hDM2. The inhibitory activities of these miniature proteins correlated with the stability of the protein fold. This emphasizes the benefit of presenting the p53AD epitope on a miniature protein scaffold.