By Wolfgang Sippl, Manfred Jung, Raimund Mannhold, Hugo Kubinyi, Gerd Folkers
Fueled by means of the services of a crew of overseas expert authors, this primary reference at the booming subject covers every little thing a drug researcher must learn about concentrating on epigenetic mechanisms of disorder.
the 1st a part of the booklet surveys present methodologies for locating and validating drug applicants that act through epigenetic mechanisms. the second one half systematically surveys recognized and suspected drug objectives in the epigenetic equipment, together with the invention and improvement of vorinostat, the 1st advertised epigenetic drug.
Read or Download Epigenetic Targets in Drug Discovery (Methods and Principles in Medicinal Chemistry, Volume 42) PDF
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Extra resources for Epigenetic Targets in Drug Discovery (Methods and Principles in Medicinal Chemistry, Volume 42)
2004) Human PAD4 regulates histone arginine methylation levels via demethylimination. Science, 306, 279–283. , Yamada, M. R. (2005) Kinetic characterization of protein arginine deiminase 4: a transcriptional corepressor implicated in the onset and progression of rheumatoid arthritis. Biochemistry, 44, 10570–10582. R. and Fast, W. (2006) Histone citrullination by protein arginine deiminase: is arginine methylation a green light or a roadblock? ACS Chemical Biology, 1, 433–441. K. M. (1999) Structure and ligand of a histone acetyltransferase bromodomain.
R. (2005) Kinetic characterization of protein arginine deiminase 4: a transcriptional corepressor implicated in the onset and progression of rheumatoid arthritis. Biochemistry, 44, 10570–10582. R. and Fast, W. (2006) Histone citrullination by protein arginine deiminase: is arginine methylation a green light or a roadblock? ACS Chemical Biology, 1, 433–441. K. M. (1999) Structure and ligand of a histone acetyltransferase bromodomain. Nature, 399, 491–496. Mellor, J. (2006) It takes a PHD to read the histone code.
4 Example of histone cross-talk on histone H3. PRMT6 and the ASH2/WDR5/MLL complex are capable of methylation of H3R2 and H3K4, respectively (a). PRMT6 cannot methylate R2 in the presence of H3K4 trimethylation (b). Asymmetric dimethylation of R2 prevents interaction of WDR5 with the H3 tail and subsequent methylation by the MLL complex (c). Trimethylation of H3K4 is a hallmark of active promoters, while asymmetric dimethylation of H3R2 is typically associated with inactive promoters. disruption of binding of the WDR5-WD40 repeats with H3K4 when H3R2 was dimethylated, a previously observed interaction .