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Summary: 47
TIDES
chimica Oggi / cHEMISTRY TOdaY - vol 27 n 2 / March/April 2009 - Focus on Tides
ABSTRACT We have employed semi-
rational design in combination
with selection systems to generate peptides interfering with a
pathogenic protein-protein interaction: the transcriptional
regulator activator Protein-1 (aP-1). Peptide inhibitors with high
interaction stability were screened and selected using either
phage display or protein-fragment complementation assays
(Pca). The specificity of interaction was further enhanced by
combining Pca with a "competitive and Negative design
Initiative" (caNdI). Selected peptides binding their target
revealed an impressive 70,000-fold increase in Kd compared to
the wild-type interaction, and major energetic differences of
up to 5.6 kcal/mol between desired and non-desired
interactions were achieved. different strategies are discussed
for targeting oncoproteins such as Jun and Fos using tailored
peptides.
Peptides tailored to interfere with
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