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 empir
ically selected which shows differential interaction with nearly all c
ompounds. By using this map to iteratively sample the chemical space,
identification of active ligands from a library of 30 000 candidate co
mpounds has been accomplished for a wide spectrum of specific protein
targets. In each case, <200 compounds were directly assayed against th
e target. Further, analysis of the fingerprint database suggests a str
ategy for effective selection of affinity chromatography ligands and s
caffolds for combinatorial chemistry. With such a system, the large nu
mbers of potential therapeutic targets emerging from genome research c
an be categorized according to ligand binding properties, complementin
g sequence based classification. (C) 1998 Elsevier Science B.V. All ri
ghts reserved.