ACS Medicinal Chemistry Letters
Letter
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In conclusion, we have discovered two lead series derived
from the hits obtained in a fragment-based screen. Compounds
within these series represent the most potent inhibitors of the
RPA70N−ATRIP protein−protein interaction reported to date,
with no detectable inhibition of RPA−ssDNA interactions. To
determine the molecular features that govern complex
formation, we have obtained cocrystal structures of the two
lead compounds, which help rationalize the SAR and provide
structural information for the design of future inhibitors.
ASSOCIATED CONTENT
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S
* Supporting Information
Synthetic procedures and assay protocols. This material is
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AUTHOR INFORMATION
Corresponding Author
■
Present Address
⊥Novartis Institutes for BioMedical Research (NIBR), Global
Discovery Chemistry, Emeryville, California 94608, United
States.
Author Contributions
∥These authors contributed equally to this work.
Funding
Funding of this research was provided in part by NIH grants
5DP1OD006933/8DP1CA174419 (NIH Director’s Pioneer
Award) to S.W.F., R01GM065484 to W.J.C., and ARRA
stimulus grant (5RC2CA148375) to Lawrence J. Marnett.
A.O.F. was supported by the Deutscher Akademischer
Austausch Dienst postdoctoral fellowship and M.D.F by the
NIH NRSA postdoctoral fellowship.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We would like to thank Dr. Dave Cortez for his intellectual
contributions in the conception of this project and providing us
with full length RPA.
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