(19) F NMR spectroscopy of labeled proteins is a sensitive method for characterizing structure, conformational dynamics, higher-order assembly, and ligand binding. Fluorination of aromatic side chains has been suggested as a labeling strategy for small-molecule ligand discovery for protein-protein interaction interfaces. Using a model transcription factor binding domain of the CREB binding protein (CBP)/p300, KIX, we report the first full small-molecule screen using protein-observed (19) F NMR spectroscopy. Screening of 508 compounds and validation by (1) H-(15) N HSQC NMR spectroscopy led to the identification of a minimal pharmacaphore for the MLL-KIX interaction site. Hit rate analysis for the CREB-KIX and MLL-KIX sites provided a metric to assess the ligandability or "druggability" of each interface informing future medicinal chemistry efforts. The structural information from the simplified spectra and data collection speed, affords a new screening tool for analysis of protein interfaces and discovery of small molecules.
This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 February 2015.
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#6,453,517
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#268
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Altmetric has tracked 34,559,526 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 61,873 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.7. This one has gotten more attention than average, scoring higher than 68% of its peers.
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We're also able to compare this research output to 693 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.
