Construction of di-scFv through a trivalent alkyne-azide 1,3-dipolar cycloaddition

Chem Commun (Camb). 2007 Feb 21:(7):695-7. doi: 10.1039/b611636a. Epub 2006 Nov 28.

Abstract

Heterofunctional azide and alkyne PEG-linkers have been synthesized and site specifically conjugated to scFv via a reactive thiol functionality; two scFv were coupled by copper catalyzed 1,3-dipolar cycloaddition to make divalent scFv (di-scFv) with an inter-scFv distance defined to provide divalent binding; antigen binding was maintained for the di-scFv construct and increased several times compared to that of the parent scFv; the cycloaddition reaction reported herein represents an important ligation strategy to covalently link macromolecular proteins and retain sensitive structural conformations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkynes
  • Antigen-Antibody Reactions
  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Azides
  • Cell Line, Tumor
  • Cross-Linking Reagents / chemistry
  • Dimerization
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin Heavy Chains / chemistry
  • Immunoglobulin Light Chains / chemistry
  • Immunoglobulin Variable Region / chemistry*
  • Immunoglobulin Variable Region / therapeutic use
  • Immunohistochemistry
  • Male
  • Protein Engineering

Substances

  • Alkynes
  • Antigens, Neoplasm
  • Azides
  • Cross-Linking Reagents
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region