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March 5th, 2025
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Columbia University
biochemistry
biorxiv

Design and Synthesis of Potent First-in-Class Histones Acetyltransferase Modulators.

Zuccarello, E.Open in Google Scholar•Mori, M.Open in Google Scholar•Calcagno, E.Open in Google Scholar•Purgatorio, R.Open in Google Scholar•Feng, Y.Open in Google Scholar•Acquarone, E.Open in Google Scholar•Francis, Y. I.Open in Google Scholar•Fa', M.Open in Google Scholar•Staniszewski, A.Open in Google Scholar•Argyrousi, E. K.Open in Google Scholaret al.

Epigenetic regulation governs gene expression through histone modifications, particularly the acetylation of lysine residues. These modifications are orchestrated by enzymes such as histone acetyltransferases (HATs) and histone deacetylases (HDACs). Among them, p300 plays a critical role in various disorders such as neurodegenerative conditions (i.e. Alzheimer s disease, and Alzheimer s Disease related dementia) and cancer (i.e. glioblastoma and B cell lymphoma). Our aim is to develop therapeutic interventions for these ailments. In this context, we designed and synthesized novel activators of the enzyme. Using an in vitro screening approach combined with structural activity relationship analysis, we successfully identified compounds that modulate histone acetylation.

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