1416446-18-8Relevant academic research and scientific papers
Solid phase synthesis of hydroxamate peptides for histone deacetylase inhibition
Wilson, David M.,Silverman, Lisa N.,Bergauer, Markus,Keshari, Kayvan R.
, p. 151 - 153 (2013/02/21)
An orthogonal protecting group strategy was devised to synthesize hydroxamic acid containing peptides for biomimetic histone deacetylase (HDAC) inhibition. The basic building block was a protected aminosuberic acid (Asu) derivative bearing a protected hydroxamate in the side-chain, related closely to HDAC inhibitors that are transition-state analogs of acetyllysine. These inhibitors include suberoylanilide hydroxamic acid (SAHA), currently being used to treat a variety of human cancers. This strategy was employed to synthesize a series of nonameric peptides related to actual HDAC substrates, derived from known sites of acetylation/deacetylation on the N-terminal tails of the histone core proteins H2A, H2B, H3, and H4. In each case the lysine residue was replaced by a hydroxamate-bearing side chain, to mimic the endogenous site of deacetylation. Mass spectrometry and high performance liquid chromatography (HPLC) confirmed the success of automated solid-phase synthesis. These results suggest facile synthesis of a new class of HDAC inhibitors that may have enhanced selectivity for specific HDAC isoforms.
