Methods of screening combinatorial libraries using immobilized or restrained receptors

The screening of combinatorial libraries for compounds with high affinity toward drug receptors is currently a major center of attention. We describe methods recently developed for library screening that involve "constrained" receptors (either immobilized onto a surface or restrained to a compartment by some physical means). These include affinity selection chromatography, ultrafiltration assays, the scintillation proximity assay, a variety of interfacial optical techniques (surface plasmon resonance and its relatives, among others), the quartz crystal microbalance, the jet ring cell, and new interferometric assays using porous silicon to immobilize the receptor. We note some trends in assay development involving assays of membrane-bound complexes, and the coupling of two analytical methods to expand the assay resolution. (C) 1999 Elsevier Science B.V. All rights reserved.