Oligomers of glycamino acid

Bioorg Med Chem. 2002 Jun;10(6):1999-2013. doi: 10.1016/s0968-0896(02)00020-2.

Abstract

Glycamino acids, a family of sugar amino acids, are derivatives of C-glycosides that possesses a carboxyl group at the C-1 position and an amino group replacing one of the hydroxyl groups at either the C-2, 3, 4, or 6 position. We have prepared a series of glucose-type glycamino acids as monomeric building blocks: these are derivatives of 2-NH(2)-Glc-beta-CO(2)H 1, 3-NH(2)-Glc-beta-CO(2)H 2, 4-NH(2)-Glc-beta-CO(2)H 3, and 6-NH(2)-Glc-beta-CO(2)H 4 and constructed four types of homo-oligomers, beta(1-->2)-linked I, beta(1-->3)-linked II, beta(1-->4)-linked III, and beta(1-->6)-linked IV, employing the well-established N-Boc and BOP strategy. CD and NMR spectral studies of these oligomers suggested that only the beta(1-->2)-linked homo-oligomer possessed a helical structure that seems to be predetermined by the linkage position. Homo-oligomers with beta(1-->2)-linkages I and beta(1-->6)-linkages IV were also subjected to O-sulfation, and these O-sulfated oligomers were found to be able, in a linkage-specific manner, to effectively inhibit L-selectin-mediated cell adhesion, HIV infection, and heparanase activity without the anticoagulant activity associated with naturally occurring sulfated polysaccharides such as heparin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Anti-HIV Agents / pharmacology
  • Carbohydrate Conformation
  • Cell Adhesion / drug effects
  • Circular Dichroism
  • Glucuronidase / antagonists & inhibitors
  • Glucuronidase / metabolism
  • Glycosides / chemical synthesis*
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • HIV / drug effects
  • Magnetic Resonance Spectroscopy
  • Oligosaccharides / chemistry*
  • Oligosaccharides / pharmacology*
  • Selectins / metabolism

Substances

  • Amino Acids
  • Anti-HIV Agents
  • Glycosides
  • Oligosaccharides
  • Selectins
  • heparanase
  • Glucuronidase