Making artificial antibodies: a format for phage display of combinatorial heterodimeric arrays.
The gene VII protein (pVII) and gene IX protein (pIX) are associated closely on the surface of filamentous bacteriophage that is opposite of the end harboring the widely exploited pIII protein. We developed a phagemid format wherein antibody heavy- and light-chain variable regions were fused to the amino termini of pVII and pIX, respectively. Significantly, the fusion proteins interacted to form a functional Fv-binding domain on the phage surface. Our approach will be applicable to the display of generic peptide and protein libraries that can form combinatorial heterodimeric arrays. Consequently, it represents a first step toward artificial antibodies and the selection of novel biological activities.
Gao
C
C
Departments of Chemistry and Molecular Biology, The Scripps Research Institute and the Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Mao
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S
Lo
C H
CH
Wirsching
P
P
Lerner
R A
RA
Janda
K D
KD
D000595:Amino Acid Sequence; D000818:Animals; D001435:Bacteriophages / Q000235:genetics; D001483:Base Sequence; D002384:Catalysis; D017931:DNA Primers; D019281:Dimerization; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics / Q000648:ultrastructure; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis* / Q000235:genetics / Q000648:ultrastructure; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis* / Q000235:genetics / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; D016133:Polymerase Chain Reaction / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics
D017931:DNA Primers; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C085706:FLAG peptide