MAKING CHEMISTRY SELECTABLE BY LINKING IT TO INFECTIVITY

The link between recognition and replication is fundamental to the ope ration of the immune system, In recent years, modeling this process in a format of phage-display combinatorial libraries has afforded a powe rful tool for obtaining valuable antibodies, However, the ability to r eadily select and isolate rare catalysts would expand the scope of lib rary technology, A technique in which phage infection controlled the l ink between recognition and replication was applied to show that chemi stry is a selectable process. An antibody that operated by covalent ca talysis to form an acyl intermediate restored phage infectivity and al lowed selection from a library in which the catalyst constituted 1 in 10(5) members. Three different selection approaches were examined for their convenience and generality. Incorporating these protocols togeth er with well known affinity labels and mechanism-based inactivators sh ould allow the procurement of a wide range of novel catalytic antibodi es.