Making chemistry selectable by linking it to infectivity.
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.
Gao
C
C
Department of Chemistry, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Lin
C H
CH
Lo
C H
CH
Mao
S
S
Wirsching
P
P
Lerner
R A
RA
Janda
K D
KD
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
D017151:Antibodies, Catalytic; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; D011993:Recombinant Fusion Proteins