brief historical overview on the discovery and characterization of bromodomains,
followed by several of the seminal discoveries of bromodomain inhibitors. The
remainder of the chapter will provide descriptions of the experimental and computational tools that are available to scientists interested in biophysical analysis of
bromodomain inhibitor discovery for developing new drugs and chemical probes.
The field of chemical epigenetics is rapidly expanding, and the goal of this chapter is
to help researchers keep abreast of the new methods being used to study this
important epigenetic protein domain.
Keywords Acetyl lysine, Biophysical assays, Bromodomain, Histones, Inhibitor
discovery, Structural biology
Abbreviations
3FY
3-Fluorotyrosine
4FF
4-Fluorophenylalanine
5FW
5-Fluorotryptophan
BET
Bromodomain and extraterminal domain
BRET
Bioluminescence resonance energy transfer
Brm
Brahma
CBP
CREB-binding protein
CPMG
Carr-Purcell-Meiboom-Gill
Cryo-TEM
Cryo-transmission electron microscopy
DSF
Differential scanning fluorimetry
FP
Fluorescence polarization
FRAP
Fluorescence recovery after photobleaching
GEM
Group epitope mapping
GST
Glutathione S-transferase
HDAC
Histone deacetylase
HTR-FRET Homogeneous time-resolved fluorescence resonance energy transfer
IC50
Inhibitory constant
ITC
Isothermal calorimetry
K d
Dissociation constant
LPS
Lipopolysaccharide
NMC
NUT-midline carcinoma
NOE
Nuclear Overhauser effect
NTA
Nickel nitrilotriacetic acid
PrOF NMR Protein-observed NMR
SPR
Surface plasmon resonance
STD
Saturation transfer difference
T 2
Transverse relaxation time
Τ c
Rotational correlation time
T m
Thermal melting temperature
288
W. C. K. Pomerantz et al.