Complementary PCAF–Coenzyme A Mutagenesis: Chemoenzymatic Synthesis of a Novel Enlarged Coenzyme A Analogue and Evaluation of Its Biological Activity

Discovered in 1996, p300/CBP-associated factor (PCAF) is a histone acetyltransferase, also known as lysine acetyltransferase 2B (KAT2B; EC No. 2.3.1.48) with crucial roles in the regulation of genes that underlie cancer, inflammation, learning and memory. PCAF catalyses the transfer of an acetyl group from acetyl coenzyme A to the e-amino group of specific lysine residues in both histone and non-histone proteins. The reverse reaction is mediated by histone deacetylases (HDACs), which remove acetyl group(s) from specific acetyl lysine residues (Scheme 1). PCAF has been shown to be a transcriptional coac-

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