Glycoconjugate Journal

, Volume 15, Issue 7, pp 697–712 | Cite as

Structure-function relations of heparin-mimetic sulfated xylan oligosaccharides: inhibition of Human Immunodeficiency Virus-1 infectivity in vitro

  • Audrey Larack Stone
  • Derek J Melton
  • Marc S Lewis


Heparins/heparan sulfates modulate the function of proteins and cell membranes in numerous biological systems including normal and disease processes in humans. Heparin has been used for many years as an anticoagulant, and anticoagulant heparin-mimetics were developed several decades ago by chemical sulfation of non-mammalian polysaccharides, e.g., an antithrombotic sulfated xylan. This pharmaceutical, which comprises a mixture of sulfated oligoxylans, also mimics most other biological actions of natural heparins in vitro, including inhibition of the human immunodeficiency virus, but the molecular basis for these actions has been unclear. Here, numerous Components of the sulfated oligoxylan mixture were isolated and when bioassayed in the case of anti-HIV-1 infectivity revealed that a structural specificity underlines the capacity of sulfated xylan to inhibit HIV-1, rather than a non-specific mechanism. Components were isolated by chromatographic fractionation through Bio-Gel P10 in 0.5M ammonium bicarbonate. This fractionation revealed an elution range associated with apparent molecular weights of ∼22 000 to <1500 relative to standard heparin and heparan sulfates and newly prepared sulfated oligosaccharide standards. Components were characterized by metachromatic absorption spectroscopy, ultracentrifugation, GlcA analysis, and potency against HIV-1 infectivity, both in the tetrazolium cytotoxicity assay and in syncytium-forming assays, in CD4-lymphocytes. Structural specificity was indicated by the differential potencies exhibited by the Components: Highest activity (cytotoxicity) was exhibited by Components in the chromatographic region ≥∼5500 in mass (50% effective (inhibitory) concentration=0.5−0.7 μg ml−1 in the first fractionation series, and 0.1−0.5 μg ml−1 in a second series). The potency declined sharply below ∼5400 in mass, but with an exception; a second structure exhibiting relatively high potency eluted among low-mass oligosaccharides which had an average size of ∼ a nonomer. Components displayed differential potencies also against the syncytium-forming infectivity of HIV-1. The high potency against syncytium-formation was retained by Components down to a minimum size of about 4500 in mass, smaller than the ≥∼5400 required above. One in ten of the β1,4-linked xyloses in the native xylan are substituted with a monomeric α1,2 DGlcA branch. We have speculated that pharmaceutical actions of sulfated xylan might be related to structures involving the α-D linked substituents and this was examined using a space-filling model of a sulfated octaxylan and by analyses of Components for GlcA content. Understanding structure/function relations in the heparin-like actions of these agents would be of general significance for the careful examination of their potential clinical usefulness in many human processes modulated by heparins, including AIDS.

Heparin-mimetic oligosaccharides anti-HIV-1 capacity of components of sulfatedxylan mass of sulfated oligosaccharides byequilibrium-ultracentrifugation 


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Copyright information

© Chapman and Hall 1998

Authors and Affiliations

  • Audrey Larack Stone
    • 1
  • Derek J Melton
    • 1
  • Marc S Lewis
    • 2
  1. 1.Laboratory of Developmental and Molecular ImmunityNational Institute of Child Health and Human Development, NIHUSA
  2. 2.Biomedical Engineering andInstrumentation Program, NCRR, NIHBethesda

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