Privileged scaffolds for blocking protein-protein interactions: 1,4-disubstituted naphthalene antagonists of transcription factor complex HOX-PBX/DNA

Bioorganic & Medicinal Chemistry Letters
Tao JiDavid G Hangauer

Abstract

Structure-based-design studies, with the crystal structure of the HOXB1-PBX1/DNA transcription factor complex, were used to identify 1,4-disubstituted naphthalenes as potential antagonists. An initial library of 32 analogs was synthesized, two of which were found to be more potent than the reported activity for a 12 amino acid peptide antagonist. Antagonists were also identified of the related BRN1/DNA and BRN2/DNA transcription factor complexes indicating that a 1,4-disubstituted naphthalene may be a privileged scaffold for preparing screening libraries targeting this family of transcription factor complexes.

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Citations

Apr 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Luca MagnaniMathieu Lupien
Oct 1, 2011·PloS One·Stéphanie DelvalRené Rezsohazy
Mar 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Leila DardaeiFrancesco Blasi
Mar 3, 2009·Acta Biomaterialia·Lorenzo AulisaJeffrey D Hartgerink
Jul 18, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tomas GonecJosef Jampilek
Apr 21, 2017·Oncotarget·Richard MorganHardev S Pandha
Aug 16, 2017·BioMed Research International·Chuanhui SunLingmei Qu
Oct 27, 2018·European Journal of Medicinal Chemistry·Subhajit MakarSushil K Singh
Jun 3, 2021·International Journal of Molecular Sciences·Maria Rita GulottaAndrea Brancale

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