Mimics of α-helices on protein surfaces have emerged as powerful reagents for antagonizing protein-protein interactions, which are difficult to target with small molecules. Here we describe the design of a cell-permeable synthetic α-helix, based on the guanine nucleotide exchange factor Sos, that interferes with Ras-Sos interaction and downregulates Ras signaling in response to receptor tyrosine kinase activation.
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This work was supported by the US National Institutes of Health (GM073943 to P.S.A. and GM078266 and an ARRA stimulus supplement (GM078266S1) to D.B.-S.). A.P. thanks New York University for the Margaret and Herman Sokol Fellowship. NMR data were collected at the New York Structural Biology Center, a Strategically Targeted Academic Research (STAR) center supported by the New York State Office of Science, Technology and Academic Research. We thank C. Lin (New York University) and A. Natarajan and R. Ghosh (City College, City University of New York) for help with the NMR studies.
The authors declare no competing financial interests.
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Patgiri, A., Yadav, K., Arora, P. et al. An orthosteric inhibitor of the Ras-Sos interaction. Nat Chem Biol 7, 585–587 (2011). https://doi.org/10.1038/nchembio.612
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