Counterion Condensation on Heparin Oligomers

Abstract

The electropherogram of native heparin shows a broad distribution of mobilities μ, which truncates abruptly at a notably high μ = 4.7 × 10(-4) cm(2) V(-1) s(-1). This highly skewed mobility distribution is also found for the 20-saccharide chain, which shows from mass spectrometry a more uniform (symmetrical) with respect to sulfation level. Since a partially degraded heparin exhibits oligomer peaks with μ> 5 × 10(-4) cm(2) V(-1) s(-1) (appearing to escape the limitation of the mobility value for native heparin), we examined the electrophoretic behavior of chain-length monodisperse heparin oligomers. Their mobilities varied inversely with the logarithm of the contour length, L, for L from 3 to 10 nm and reached an asymptotic limit for L > 20 nm. The generality of this effect was indicated by similar behavior for oligomers of poly(styrene sulfonate). A recent theory of polyelectrolyte end effects (Manning, G. S. Macromolecules2008, 41, 6217-6227), in which chain termini exhibit reduced counterion condensation was found to quantitatively account for these results. A qualitative explanation for the anomalously high value of μ of native heparin, 10-20% higher than those seen for synthetic polyelectrolytes of higher linear charge density, is suggested on the basis of similar junction effects (Manning, G. S. Macromolecules2008, 41, 6217-6227), which reduce counterion condensation at the interfaces of regions of high and low sulfation. We suggest that these effects should be considered in models for the biofunctionality of the regulated high and low sulfation (NS/NA) domains of heparan sulfate.

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Heparin Decamer Bridges a Growth Factor and an Oligolysine by Different Charge-Driven Interactions

“…A more recent theoretical result by Manning for oligo-polyelectrolytes is the diminution of condensation at and near chain ends, 47 subsequently verified by Minsky et al for heparin oligomers. 22 Representation of the heparin disaccharide structure (Scheme 1, above) neglecting positional variations of sulfation leads to visualization of the chain as treated in the condensation model (Scheme 1, below), with the condensed counterion layer depleted at chain ends. If those ions are involved in the oligolysine binding process, the strongest K 4 binding site would comprise chain units far from the ends of dp10, that is, saccharides 3−8 (contour length ∼ 3 nm).…”