title: Making chemistry selectable by linking it to infectivity.
abstract: The link between recognition and replication is fundamental to the operation of the immune system. In recent years, modeling this process in a format of phage-display combinatorial libraries has afforded a powerful tool for obtaining valuable antibodies. However, the ability to readily select and isolate rare catalysts would expand the scope of library technology. A technique in which phage infection controlled the link between recognition and replication was applied to show that chemistry is a selectable process. An antibody that operated by covalent catalysis to form an acyl intermediate restored phage infectivity and allowed 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 together with well known affinity labels and mechanism-based inactivators should allow the procurement of a wide range of novel catalytic antibodies.
authors.affiliation: Department of Chemistry, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: C
authors.initials: C
authors.lastname: Gao
authors.forename: C H
authors.initials: CH
authors.lastname: Lin
authors.forename: C H
authors.initials: CH
authors.lastname: Lo
authors.forename: S
authors.initials: S
authors.lastname: Mao
authors.forename: P
authors.initials: P
authors.lastname: Wirsching
authors.forename: R A
authors.initials: RA
authors.lastname: Lerner
authors.forename: K D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D017151:Antibodies, Catalytic / Q000235:genetics*; D001435:Bacteriophages / Q000472:pathogenicity; D001483:Base Sequence; D006378:Helper Viruses; D007128:Immunoglobulin Fragments / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008967:Molecular Biology / Q000379:methods*; D008969:Molecular Sequence Data; D019151:Peptide Library; D011993:Recombinant Fusion Proteins; D012641:Selection, Genetic
chemical_list: D017151:Antibodies, Catalytic; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; D011993:Recombinant Fusion Proteins