摘要 |
<p>This invention combines the unique antiplatelet effects of S-nitrosothiols and the antiadhesive properties of fragments of vWF in the Al domain to provide unique molecules that exploit both of these properties. Preferred molecules comprise a fragment of Al (ala444-asp730) in which arginine at position 545 is replaced by cysteine (the most frequent von Willebrand disease type 2b mutation) that has been discovered to impair platelet adhesion, and to exhibit antithrombotic activity in vivo. This cysteine residue may be S-nitrosated to produce a novel molecule that has the potential for impairing platelet adhesion as well as activation/aggregation, and such molecules form the basis of a novel therapeutic method for impairing platelet responses following vascular injury or in other thrombotic disorders according to this invention.</p> |