Unnatural ligands for engineered proteins: new tools for chemical genetics.
Small molecules that modulate the activity of biological signaling molecules can be powerful probes of signal transduction pathways. Highly specific molecules with high affinity are difficult to identify because of the conserved nature of many protein active sites. A newly developed approach to discovery of such small molecules that relies on protein engineering and chemical synthesis has yielded powerful tools for the study of a wide variety of proteins involved in signal transduction (G-proteins, protein kinases, 7-transmembrane receptors, nuclear hormone receptors, and others). Such chemical genetic tools combine the advantages of traditional genetics and the unparalleled temporal control over protein function afforded by small molecule inhibitors/activators that act at diffusion controlled rates with targets.
Bishop
A
A
Department of Chemistry, Princeton University, New Jersey 08544, USA.
Buzko
O
O
Heyeck-Dumas
S
S
Jung
I
I
Kraybill
B
B
Liu
Y
Y
Shah
K
K
Ulrich
S
S
Witucki
L
L
Yang
F
F
Zhang
C
C
Shokat
K M
KM
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020558:GTP Phosphohydrolases / Q000737:chemistry; D005821:Genetic Techniques; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000235:genetics; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009218:Myosins / Q000737:chemistry / Q000235:genetics; D015202:Protein Engineering; D011494:Protein Kinases / Q000737:chemistry; D011506:Proteins / Q000138:chemical synthesis; D015398:Signal Transduction
D008024:Ligands; D011506:Proteins; D011494:Protein Kinases; D020558:GTP Phosphohydrolases; D009218:Myosins; D016547:Kinesins