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J Biol Chem, Vol. 274, Issue 12, 7656-7667, March 19, 1999
,
From the Sulfated fucans are among the most widely studied
of all the sulfated polysaccharides of non-mammalian origin that
exhibit biological activities in mammalian systems. Examples of these polysaccharides extracted from echinoderms have simple structures, composed of oligosaccharide repeating units within which the residues differ by specific patterns of sulfation among different species. In
contrast the algal fucans may have some regular repeating structure but
are clearly more heterogeneous when compared with the echinoderm fucans. The structures of the sulfated fucans from brown algae also
vary from species to species. We compared the anticoagulant activity of
the regular and repetitive fucans from echinoderms with that of the
more heterogeneous fucans from three species of brown algae. Our
results indicate that different structural features determine not only
the anticoagulant potency of the sulfated fucans but also the mechanism
by which they exert this activity. Thus, the branched fucans from brown
algae are direct inhibitors of thrombin, whereas the linear fucans from
echinoderms require the presence of antithrombin or heparin cofactor II
for inhibition of thrombin, as reported for mammalian
glycosaminoglycans. The linear sulfated fucans from echinoderms have an
anticoagulant action resembling that of mammalian dermatan sulfate and
a modest action through antithrombin. A single difference of one
sulfate ester per tetrasaccharide repeating unit modifies the
anticoagulant activity of the polysaccharide markedly. Possibly the
spatial arrangements of sulfate esters in the repeating tetrasaccharide unit of the echinoderm fucan mimics the site in dermatan sulfate with
high affinity for heparin cofactor II.
Laboratório de Tecido Conjuntivo,
Hospital Universitário and Departamento de Bioquímica
Médica, Centro de Ciências da Saúde, Universidade
Federal do Rio de Janeiro, Caixa Postal 68041, Rio de Janeiro,
RJ 21941-590, Brazil and § National Institute for
Biological Standards and Control, South Mimms, Potters Bar,
Hertfordshire EN6 3QG, United Kingdom
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