Polysulfated derivatives of beta-cyclodextrin and myo-inositol as potent inhibitors of the interaction between L-selectin and peripheral addressin: implying a requirement for highly clustered sulfate groups

Biochemical and Biophysical Research Communications
K ShailubhaiG S Jacob

Abstract

We have utilized an in vitro assay that measures the binding of an L-selectin-human Fc chimera (LS-Fc) to [35S]sulfate labelled peripheral addressin (PNAd), a 120 kDa glycoprotein ligand for L-selectin in porcine lymph nodes, to evaluate inhibitory properties of a small group of sulfated derivatives of beta-cyclodextrin (beta-CD), sLe(x) and myo-inositol to their non-sulfated counterparts were studied. We found that hepta-sulfated beta-CD (IC50 = 0.2 mM) strongly inhibited the binding of L-selectin to PNAd. In contrast, the monosulfated beta-CD was a poor inhibitor, displaying < 10% inhibition at 0.5 mM and beta-CD was not active as an inhibitor. Similarly, inositol hexakissulfate, a compound containing six sulfate groups on the inositol ring displayed an inhibition of about 61% at 0.5 mM concentration, whereas the non-sulfated myoinositol was not inhibitory. These findings provide evidence that clustering of sulfate groups enhances affinity of molecules for binding to L-selectin.

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