A chemical tool for in vitro and in vivo precipitation of lysine methyltransferase G9a.
Here we report the design, synthesis, and biochemical characterization of a new chemical tool, UNC0965. UNC0965 is a biotinylated version of our previously reported G9a chemical probe, UNC0638. Importantly, UNC0965 maintains high in vitro potency and is cell penetrant. The biotinylated tag of UNC0965 enables "chemiprecipitation" of G9a from whole cell lysates. Further, the cell penetrance of UNC0965 allowed us to explore the localization of G9a on chromatin both in vitro and in vivo through chemical inhibitor-based chromatin immunoprecipitation (chem-ChIP).
Center for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC 27599 (USA).
Kyle D
KD
Konze
Samantha G
SG
Pattenden
Feng
F
Liu
Dalia
D
Barsyte-Lovejoy
Fengling
F
Li
Jeremy M
JM
Simon
Ian J
IJ
Davis
Masoud
M
Vedadi
Jian
J
Jin
D001710:Biotin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D019921:Biotinylation; D011232:Chemical Precipitation; D002843:Chromatin / Q000201:enzymology; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D057809:HEK293 Cells; D006649:Histocompatibility Antigens / Q000737:chemistry* / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry*
D002843:Chromatin; D006649:Histocompatibility Antigens; D011799:Quinazolines; C000592884:UNC0965; D001710:Biotin; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase
G9a; chromatin; enzymes; lysine methyltransferase; medicinal chemistry