Abstract
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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04 August 2011
In the version of this article initially published online, the description of the control analog HBS 7 incorrectly stated that "three alanines were replaced with residues that are important for interaction: Phe929, Glu942 and Asn944." It should have said that in this analog "the residues that are important for interaction, Phe929, Glu942 and Asn944, were replaced with alanine residues." The error has been corrected for the print, PDF and HTML versions of this article.
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Acknowledgements
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.
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A.P., K.K.Y., P.S.A. and D.B.-S. designed experiments, analyzed data and wrote the paper, and A.P. and K.K.Y. performed experiments.
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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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DOI: https://doi.org/10.1038/nchembio.612
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