Synthesis of chitooligomer-based glycoconjugates and their binding to the rat natural killer cell activation receptor NKR-P1

Glycoconj J. 2001 Oct;18(10):817-26. doi: 10.1023/a:1021111703443.

Abstract

NKR-P1 protein is an important activating receptor at the surface of the rat natural killer cells. GlcNAc and chitooligomers were identified as strong activation ligands in vitro and in vivo. Their clustering brings about increase of their affinity to the NKR-P1 by 3-6 orders. Here we describe novel methodology for preparation of neoglycoproteins based on BSA carrying the chitooligomers (n = 2-5). Further on we developed novel methodology of the coupling of glycosylamines via aromatic-SCN activated linker both to protein or synthetic cores. Inhibition studies of chitooligomer glycoconjugates with the NKR-P1 receptor show that our neoglycoproteins are very strong ligands with high binding affinity (-log IC(50) = 13-15). In analogy with our previous observations with GlcNAc clustered on protein or PAMAM backbones the synthetic chitooligomer clusters should provide considerably better ligands in the in vivo antitumor treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Animals
  • Antigens, Surface / metabolism*
  • Cattle
  • Chitin / chemistry
  • Chromatography / methods
  • Glycoproteins / chemical synthesis*
  • Glycoproteins / metabolism*
  • Immunoblotting
  • Inhibitory Concentration 50
  • Isothiocyanates / chemistry
  • Killer Cells, Natural / metabolism*
  • Lectins, C-Type / metabolism*
  • Ligands
  • N-Acetylneuraminic Acid / metabolism
  • NK Cell Lectin-Like Receptor Subfamily B
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Rats
  • Serum Albumin, Bovine / chemistry
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
  • Thioglycosides / chemical synthesis

Substances

  • Amines
  • Antigens, Surface
  • Glycoproteins
  • Isothiocyanates
  • Lectins, C-Type
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily B
  • Thioglycosides
  • Chitin
  • Serum Albumin, Bovine
  • N-Acetylneuraminic Acid