Making artificial antibodies: a format for phage display of combinatorial heterodimeric arrays

Proc Natl Acad Sci U S A. 1999 May 25;96(11):6025-30. doi: 10.1073/pnas.96.11.6025.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacteriophages / genetics
  • Base Sequence
  • Catalysis
  • DNA Primers
  • Dimerization
  • Epitopes
  • Immunoglobulin Heavy Chains / biosynthesis*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / ultrastructure
  • Immunoglobulin Light Chains / biosynthesis*
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light Chains / ultrastructure
  • Immunoglobulin Variable Region / biosynthesis*
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / ultrastructure
  • Mice
  • Microscopy, Electron
  • Oligopeptides
  • Peptide Library*
  • Peptides
  • Polymerase Chain Reaction / methods
  • Recombinant Fusion Proteins / biosynthesis
  • Restriction Mapping
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics

Substances

  • DNA Primers
  • Epitopes
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region
  • Oligopeptides
  • Peptide Library
  • Peptides
  • Recombinant Fusion Proteins
  • Viral Proteins
  • FLAG peptide