Design, synthesis, and in vitro activity of peptidomimetic inhibitors of myeloid differentiation factor 88.

J Med Chem 2008 Mar 15;51(5):1189-202. Epub 2008 Feb 15.

Sigma-Tau Industrie, Pomezia, Italy.

We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide Ac-RDVLPGT-NH 2, belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The ability of the peptidomimetics to inhibit protein-protein interaction was assessed by yeast 2-hybrid assay and further validated in a mammalian cell system by evaluating the inhibition of NF-kappaB activation, a transcription factor downstream of MyD88 signaling pathway that allows production of essential effector molecules for immune and inflammatory responses.

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http://dx.doi.org/10.1021/jm070723uDOI Listing
March 2008

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