A remarkable complex of double-stranded DNA, PU.1 protein, and a pyrrole-imidazole polyamide is described. PU.1 is implicated in many cancers and the ability to control its DNA binding is important. Inhibitors of PU.1-DNA binding are also described.
PU.1. is often referred to as an undruggable target, but we describe numerous inhibitors that prevent it from binding to DNA and remove bound PU.1 from DNA. We also describe a ternary complex of DNA, PU.1, and a pyrrole-imidazole polyamide that is stabilized by the formation of the ternary complex.
This is an exciting collaboration among three groups, depending on the PU.1 expertise of Gregory Poon, the biophysics expertise and measurements of W. David Wilson and his group, and the synthetic chemistry of James Bashkin. Both Poon and Wilson are from Georgia State University while Bashkin is from the University of Missouri-St. Louis.Dr. James Bashkin, D. Phil.
Biochimie 2019 Dec 21;167:1-11. Epub 2019 Aug 21.
Department of Chemistry, Georgia State University, Atlanta, GA, 30303, USA. Electronic address:
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