Naturally-occurring
fibrinogen receptor antagonists and
platelet aggregation inhibitors that are found in
snake venom (
disintegrins) and leeches share many common features, including an RGD sequence, high
cysteine content, and low molecular weight. There are, however, significant selectivity and potency differences. We compared the effect of three
proteins on platelet function:
albolabrin, a 7.5 kDa
disintegrin,
eristostatin, a 5.4 kDa
disintegrin in which part of the
disintegrin domain is deleted, and
decorsin, a 4.5 kDa non-
disintegrin derived from the leech Macrobdella decora, which has very little sequence similarity with either
disintegrin.
Decorsin was about two times less potent than
albolabrin and six times less potent than
eristostatin in inhibiting
ADP-induced human platelet aggregation. It had a different pattern of interaction with
glycoprotein IIb/IIIa as compared to the two
disintegrins.
Decorsin bound with a low affinity to resting platelets (409 nM) and to
ADP-activated platelets (270 nM), and with high affinity to
thrombin activated platelets (74 nM). At concentrations up to 685 nM, it did not cause expression of a
ligand-induced binding site
epitope on the beta 3 subunit of the GPIIb/IIIa complex. It did not significantly inhibit isolated GPIIb/IIIa binding to immobilized
von Willebrand Factor. At low doses (1.5-3.0 micrograms/mouse),
decorsin protected mice against death from
pulmonary thromboembolism, showing an effect similar to
eristostatin. This suggested that
decorsin is a much more potent inhibitor of platelet aggregation in vivo than in vitro, and it may have potential as an
antiplatelet drug.