The Use of Combinatorial Libraries to Identify Ligands That Interact with Surface Receptors in Living Cells

Abstract

Interactions between combinatorial libraries and various selector proteins, such as antibodies and receptors, have been demonstrated either in solution (1) or while the selector proteins were bound to a solid support (2–5). Before the introduction of the library to a selector protein, the latter is purified in order to avoid nondesirable interactions between various members of the library and nonrelevant contaminants. However, purification of some proteins 1s difficult to achieve, and might be deleterious to then biological activity. It is therefore important to develop methods that employ combinatorial libraries in combination with nonpurified or partially purified selector proteins. In this regard, Jayawickreme and Lerner developed a technique for screening combinatorial libraries employing recombinant receptors expressed in the plasma membrane of transfected melanophors (6,7 and Chapters 13,14). Their technique is based on the biological activity of the expressed receptors and it enables the selection of library members with agonistic or antagonistic activities.