Characterization of new modular nanotransporters with albumin-binding domain

Dokl Biochem Biophys. 2017 Jan;472(1):81-83. doi: 10.1134/S1607672917010203. Epub 2017 Apr 19.

Abstract

The albumin-binding domain (ABD) with a site for its cleavage by tumor proteases was inserted in the structure of modular nanotransporters (MNTs), chimeric proteins for the delivery of anticancer drugs into the nuclei of cancer cells. The effectiveness of this cleavage was tested in both variants of created construct: "pure" ABD-MNT and the complex with albumin. The introduction of the ABD module into MNTs had no effect on the binding of MNT with receptors on the surface of the target cancer cells and on the preferential accumulation of MNTs in the nuclei of these cells. The use of thermophoresis allowed us to determine the equilibrium dissociation constants of the ABD-MNT complex with bovine and human serum albumins.

MeSH terms

  • Active Transport, Cell Nucleus
  • Albumins / genetics*
  • Albumins / metabolism
  • Binding Sites
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Diphtheria Toxin / genetics
  • Diphtheria Toxin / metabolism
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism
  • Protein Binding
  • Protein Engineering / methods
  • Recombinant Fusion Proteins / genetics*
  • Recombinant Fusion Proteins / metabolism

Substances

  • Albumins
  • Diphtheria Toxin
  • Karyopherins
  • Recombinant Fusion Proteins
  • Epidermal Growth Factor
  • Peptide Hydrolases