1219184-45-8Relevant articles and documents
Strategy for "Detoxification" of a cancer-derived histone mutant based on mapping its interaction with the methyltransferase PRC2
Brown, Zachary Z.,Müller, Manuel M.,Jain, Siddhant U.,Allis, C. David,Lewis, Peter W.,Muir, Tom W.
supporting information, p. 13498 - 13501 (2015/02/02)
The histone methyltransferase PRC2 plays a central role in genomic stability and cellular development. Consequently, its misregulation has been implicated in several cancers. Recent work has shown that a histone H3 mutant, where the PRC2 substrate residue Lys27 is replaced by methionine, is also associated with cancer phenotypes and functions as an inhibitor of PRC2. Here we investigate the mechanism of this PRC2 inhibition through kinetic studies and photo-cross-linking. Efficient inhibition is dependent on (1) hydrophobic lysine isosteres blocking the active site, (2) proximal residues, and (3) the H3 tail forming extensive contacts with the EZH2 subunit of PRC2. We further show that naturally occurring post-translational modifications of the same H3 tail, both proximal and distal to K27M, can greatly diminish the inhibition of PRC2. These results suggest that this potent gain of function mutation may be "detoxified by modulating alternate chromatin modification pathways.
Tandem Ru-alkylidene-catalysed cross metathesis/hydrogenation: Synthesis of lipophilic amino acids
Wang, Zhen J.,Spiccia, Nicolas D.,Jackson, W. Roy,Robinson, Andrea J.
, p. 470 - 476 (2013/08/23)
Highly efficient synthesis of lipidic amino acids can be achieved via Ru-alkylidene-catalysed cross metathesis of long chain alkenes with commercially available allylglycine. The resultant unsaturated analogues can be then optionally hydrogenated under mi
Total synthesis of cyclocitropside A and its conversion to cyclocitropsides B and C via asparagine deamidation
Thompson, Robert E.,Payne, Richard J.,Jolliffe, Katrina A.
supporting information, p. 5110 - 5113 (2013/01/15)
The total syntheses of three closely related cyclic peptide natural products, cyclocitropsides A-C, are described. Cyclocitropside A could be readily converted into cyclocitropsides B and C through an asparagine deamidation pathway, indicating that this is a plausible biosynthetic route to these compounds.
