Protein affinity map of chemical space.
Affinity fingerprinting is a quantitative method for mapping chemical space based on binding preferences of compounds for a reference panel of proteins. An effective reference panel of <20 proteins can be empirically selected which shows differential interaction with nearly all compounds. By using this map to iteratively sample the chemical space, identification of active ligands from a library of 30,000 candidate compounds has been accomplished for a wide spectrum of specific protein targets. In each case, <200 compounds were directly assayed against the target. Further, analysis of the fingerprint database suggests a strategy for effective selection of affinity chromatography ligands and scaffolds for combinatorial chemistry. With such a system, the large numbers of potential therapeutic targets emerging from genome research can be categorized according to ligand binding properties, complementing sequence based classification.
Kauvar
L M
LM
Terrapin Technologies, Inc., San Francisco, CA 94080, USA.
Villar
H O
HO
Sportsman
J R
JR
Higgins
D L
DL
Schmidt
D E
DE
D002846:Chromatography, Affinity / Q000379:methods*; D003628:Database Management Systems; D005454:Fluorescence Polarization; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012015:Reference Standards
D008024:Ligands; D011506:Proteins