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• W2017788703 abstract "Abstract The identification of binding sites for small molecules in genomic DNA is important in various applications. Previously, we demonstrated rapid transcriptional activation by our small molecule SAHA‐PIP. However, it was not clear whether the strong biological effects exerted by SAHA‐PIP were attributable to its binding specificity. Here, we used high‐throughput sequencing (Bind‐n‐seq) to determine the binding specificity of SAHA‐PIPs. Sequence specificity bias was determined for SAHA‐PIPs ( 3 and 4 ), and this showed enhanced 6 bp sequence‐specific binding compared with hairpin PIPs ( 1 and 2 ). This finding allowed us to investigate the role of the β‐alanine that links SAHA to PIP, and led in turn to the design of ββ‐PIPs ( 5 and 6 ), which showed enhanced binding specificity. Overall, we demonstrated the importance of β‐moieties for the binding specificity of PIPs and the use of cost‐effective high‐throughput screening of these small molecules for binding to the DNA minor groove." @default.
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• W2017788703 date "2014-11-04" @default.
• W2017788703 modified "2023-10-18" @default.
• W2017788703 title "Next-Generation Sequencing Studies Guide the Design of Pyrrole-Imidazole Polyamides with Improved Binding Specificity by the Addition of β-Alanine" @default.
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• W2017788703 doi "https://doi.org/10.1002/cbic.201402497" @default.
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