Cloning and characterization of Scavidin, a fusion protein for the targeted delivery of biotinylated molecules

J Biol Chem. 2002 Mar 8;277(10):8545-50. doi: 10.1074/jbc.M109431200. Epub 2001 Dec 12.

Abstract

We have constructed a novel fusion protein "Scavidin" consisting of the macrophage scavenger receptor class A and avidin. The Scavidin fusion protein is transported to plasma membranes where the avidin portion of the fusion protein binds biotin with high affinity and forms the basis for the targeted delivery of biotinylated molecules. Subcellular fractionation analysis, immunostaining, and electron microscopy demonstrated endosomal localization of the fusion protein. According to pulse-labeling and cross-linking studies Scavidin is found as monomers (55 kDa), dimers, and multimers, of which the 220-kDa form was the most abundant. The biotin binding capacity and active endocytosis of the biotinylated ligands were demonstrated in rat malignant glioma. Local Scavidin gene transfer to target tissues could have general utility as a universal tool to deliver biotinylated molecules at systemic low concentrations for therapeutic and imaging purposes, whereby high local concentration is achieved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avidin / chemistry*
  • Avidin / genetics
  • Avidin / metabolism
  • Biotinylation*
  • Blotting, Northern
  • Blotting, Western
  • Cell Membrane / metabolism*
  • Cloning, Molecular
  • Cross-Linking Reagents / pharmacology
  • Dimerization
  • Endocytosis
  • Gene Transfer Techniques
  • Genetic Vectors
  • Glioma / metabolism
  • Immunohistochemistry
  • Ligands
  • Microscopy, Fluorescence
  • Microscopy, Immunoelectron
  • Models, Genetic
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / genetics
  • Receptors, Scavenger
  • Recombinant Fusion Proteins / chemistry*
  • Recombinant Fusion Proteins / genetics
  • Retroviridae / genetics
  • Scavenger Receptors, Class A
  • Transduction, Genetic
  • Tumor Cells, Cultured

Substances

  • Cross-Linking Reagents
  • Ligands
  • Receptors, Immunologic
  • Receptors, Scavenger
  • Recombinant Fusion Proteins
  • Scavenger Receptors, Class A
  • scavidin
  • Avidin