Design, Synthesis, and In Vitro Activity of Peptidomimetic Inhibitors of Myeloid Differentiation Factor 88

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• 作者：Nicola Fantò ; Grazia Gallo ; Andrea Ciacci ; Mauro Semproni ; Davide Vignola ; Marco Quaglia ; Valentina Bombardi ; Domenico Mastroianni ; M. Pia Zibella ; Giancarlo Basile ; Marica Sassano ; Vito Ruggiero
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：March 13, 2008
• 年：2008
• 卷：51
• 期：5
• 页码：1189 - 1202
• 全文大小：770K
• 年卷期：v.51,no.5(March 13, 2008)
• ISSN：1520-4804

文摘

We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide Ac-RDVLPGT-NH₂, 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-κB activation, a transcription factor downstream of MyD88 signaling pathway that allows production of essential effector molecules for immune and inflammatory responses.