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

  • J Med Chem. 2008 Mar 13;51(5):1189-202. doi: 10.1021/jm070723u.
Nicola Fantò  1 ,  Grazia Gallo ,  Andrea Ciacci ,  Mauro Semproni ,  Davide Vignola ,  Marco Quaglia ,  Valentina Bombardi ,  Domenico Mastroianni ,  M Pia Zibella ,  Giancarlo Basile ,  Marica Sassano ,  Vito Ruggiero ,  Rita De Santis ,  Paolo Carminati
Affiliations
PMID: 18275134 DOI: 10.1021/jm070723u
Abstract

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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