Robust and systematic drug screening method using chemical arrays and the protein library: identification of novel inhibitors of carbonic anhydrase II.
The identification of specific interactions between small molecules and human proteins of interest is a fundamental step in chemical biology and drug development. Here we describe an efficient method to obtain novel binding ligands of human proteins by a chemical array approach. Our method includes large-scale ligand screening with two libraries, proteins and chemicals, the use of cell lysates that express proteins of interest fused with red fluorescent protein, and high-throughput screening by merged display analysis, which removes false positive signals from array experiments. Using our systematic platform, we detected novel inhibitors of carbonic anhydrase II. It is suggested that our systematic platform is a rapid and robust approach to screen novel ligands for human proteins of interest.
Antibiotics Laboratory and Chemical Biology Department, RIKEN, Saitama, Japan.
Isao
I
Miyazaki
Siro
S
Simizu
Harumi
H
Ichimiya
Makoto
M
Kawatani
Hiroyuki
H
Osada
D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015698:Genomic Library; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D019151:Peptide Library; D011485:Protein Binding; D020123:Sirolimus / Q000378:metabolism; D013329:Structure-Activity Relationship; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism
D004791:Enzyme Inhibitors; D008024:Ligands; D019151:Peptide Library; D024402:Carbonic Anhydrase II; D022061:Tacrolimus Binding Protein 1A; D020123:Sirolimus