Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 48, Issue 4, Pages 1269-1273Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm0492960
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Funding
- NHLBI NIH HHS [R01 HL069975] Funding Source: Medline
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Accelerated antithrombin inhibition of procoagulant enzymes has been exclusively achieved with polysulfated polysaccharides. We reasoned that antithrombin activation should be possible with nonsulfated activators based only on carboxylic acid groups. As a proof of the principle, linear poly(acrylic acid)s were found to bind to antithrombin and accelerate inhibition of factor Xa and thrombin. Our work demonstrates that molecules completely devoid of sulfate groups can activate antithrombin effectively and, more importantly, suggests that it may be possible to develop orally bioavailable, carboxylate-based antithrombin activators.
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