Water accessibility, aggregation, and motional features of polysaccharide-protein conjugate vaccines

Biophys J. 2004 Jan;86(1 Pt 1):3-9. doi: 10.1016/S0006-3495(04)74078-3.

Abstract

A relaxometric investigation of a nontoxic mutant of diphtheria toxin and of its conjugates with capsular polysaccharides of different groups of Neisseria meningitidis was performed. The insertion of polysaccharides chains alters dramatically the hydrodynamic properties of the protein. The model-free analysis of the (1)H nuclear magnetic relaxation dispersion profiles of their water solutions shows: i), a reduced protein hydration with respect to the carrier protein alone; ii), a much larger flexibility of the conjugates with respect to a compact macromolecule of the same molecular weight; and iii), a strong tendency to aggregate. The above findings are largely independent on the nature of the polysaccharide and thus provide a fairly general picture of the dynamic properties of glycoconjugate proteins.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Capsules / chemistry*
  • Bacterial Capsules / classification
  • Binding Sites
  • Diphtheria Toxin / chemistry*
  • Diphtheria-Tetanus Vaccine / chemistry
  • Macromolecular Substances
  • Models, Chemical*
  • Molecular Weight
  • Motion
  • Neisseria meningitidis / chemistry*
  • Polysaccharides, Bacterial / chemistry
  • Protein Binding
  • Structure-Activity Relationship
  • Vaccines, Conjugate / chemistry
  • Water / chemistry*

Substances

  • Diphtheria Toxin
  • Diphtheria-Tetanus Vaccine
  • Macromolecular Substances
  • Polysaccharides, Bacterial
  • Vaccines, Conjugate
  • Water