Synthesis of chondroitin/dermatan sulfate-like oligosaccharides and evaluation of their protein affinity by fluorescence polarization

Org Biomol Chem. 2013 Jun 7;11(21):3510-25. doi: 10.1039/c3ob40306h. Epub 2013 Apr 17.

Abstract

Here, we present a novel approach for the chemical synthesis of chondroitin and dermatan sulfate oligosaccharides. A key point of this strategy is the preparation and use of an N-trifluoroacetyl galactosamine building block containing a 4,6-O-di-tert-butylsilylene group. Glycosylation reactions proceeded in good yields (74-91%) with our protecting group distribution. Using this approach, we have synthesized, for the first time, a chondroitin/dermatan sulfate-like tetrasaccharide that contains both types of uronic acids, D-glucuronic and L-iduronic acid. Moreover, we have employed a fluorescence polarization competition assay to evaluate the interactions between the synthesized oligosaccharides and FGF-2 (basic fibroblast growth factor). Our results show that this method, using standard instrumentation and minimal sample consumption, is a powerful tool for the rapid analysis of the glycosaminoglycan affinity for proteins in solution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chondroitin Sulfates / chemical synthesis*
  • Chondroitin Sulfates / chemistry
  • Dermatan Sulfate / chemical synthesis*
  • Dermatan Sulfate / chemistry
  • Fibroblast Growth Factor 2 / chemistry
  • Fluorescence Polarization
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Protein Binding

Substances

  • Fibroblast Growth Factor 2
  • Dermatan Sulfate
  • Chondroitin Sulfates