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dc.contributor.authorClemons, Paul A.
dc.contributor.authorBodycombe, Nicole E.
dc.contributor.authorCarrinski, Hyman A.
dc.contributor.authorWilson, J. Anthony
dc.contributor.authorShamji, Alykhan F.
dc.contributor.authorWagner, Bridget K.
dc.contributor.authorKoehler, Angela N.
dc.contributor.authorSchreiber, Stuart L.
dc.date.accessioned2019-10-03T14:38:02Z
dc.date.issued2010
dc.identifier.citationClemons, P. A., N. E. Bodycombe, H. A. Carrinski, J. A. Wilson, A. F. Shamji, B. K. Wagner, A. N. Koehler, and S. L. Schreiber. 2010. “Small Molecules of Different Origins Have Distinct Distributions of Structural Complexity That Correlate with Protein-Binding Profiles.” Proceedings of the National Academy of Sciences 107 (44): 18787–92. https://doi.org/10.1073/pnas.1012741107.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41461170*
dc.description.abstractUsing a diverse collection of small molecules generated from a variety of sources, we measured protein-binding activities of each individual compound against each of 100 diverse (sequence-unrelated) proteins using small-molecule microarrays. We also analyzed structural features, including complexity, of the small molecules. We found that compounds from different sources (commercial, academic, natural) have different protein-binding behaviors and that these behaviors correlate with general trends in stereochemical and shape descriptors for these compound collections. Increasing the content of sp(3)-hybridized and stereogenic atoms relative to compounds from commercial sources, which comprise the majority of current screening collections, improved binding selectivity and frequency. The results suggest structural features that synthetic chemists can target when synthesizing screening collections for biological discovery. Because binding proteins selectively can be a key feature of high-value probes and drugs, synthesizing compounds having features identified in this study may result in improved performance of screening collections.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleSmall molecules of different origins have distinct distributions of structural complexity that correlate with protein-binding profiles
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorSchreiber, Stuart L.::80f648d0514e642a8f97bb9b12b10db7::600
dc.date.available2019-10-03T14:38:02Z
dash.workflow.comments1Science Serial ID 90615
dc.identifier.doi10.1073/pnas.1012741107
dash.source.volume107;44
dash.source.page18787


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