End-Site-Specific Conjugation of Enoxaparin and Tetradeoxycholic Acid Using Nonenzymatic Glycosylation for Oral Delivery.
J Med Chem
; 59(23): 10520-10529, 2016 12 08.
Article
em En
| MEDLINE
| ID: mdl-27933952
ABSTRACT
Heparin and low molecular weight heparins (LMWHs) have been the drug of choice for the treatment or the prevention of thromboembolic disease. Different methods are employed to prepare the LMWHs that are clinically approved for the market currently. In particular, enoxaparin, which has a reducing sugar moiety at the end-site of polysaccharide, is prepared by alkaline depolymerization. Focusing on this end-site-specific activity of LMWHs, we conjugated the tetraoligomer of deoxycholic acid (TetraDOCA; TD) at the end-site of enoxaparin via nonenzymatic glycosylation reaction. The end-site-specific conjugation is important for polysaccharide drug development because of the heterogeneity of polysaccharides. This study also showed that orally active enoxaparin and tetraDOCA conjugate (EnoxaTD) had therapeutic effect on deep vein thrombosis (DVT) without bleeding in animal models. Considering the importance of end-specific conjugation, these results suggest that EnoxaTD could be a drug candidate for oral heparin development.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Cólicos
/
Sistemas de Liberação de Medicamentos
/
Enoxaparina
/
Trombose Venosa
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article