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 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.