title: End-Site-Specific Conjugation of Enoxaparin and Tetradeoxycholic Acid Using Nonenzymatic Glycosylation for Oral Delivery.
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.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul 151-742, South Korea.|Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology , Seoul 136-791, South Korea.
authors.forename: Jooho
authors.initials: J
authors.lastname: Park
authors.affiliation: B&L DELIPHARM , Seoul 151-742, South Korea.
authors.forename: Ok Cheol
authors.initials: OC
authors.lastname: Jeon
authors.affiliation: ST Pharm Research & Development Center , HyeopRyeok Road, Siheung-Si, Gyeonggi-do, South Korea.
authors.forename: Jisuk
authors.initials: J
authors.lastname: Yun
authors.affiliation: ST Pharm Research & Development Center , HyeopRyeok Road, Siheung-Si, Gyeonggi-do, South Korea.
authors.forename: Hwajung
authors.initials: H
authors.lastname: Nam
authors.affiliation: ST Pharm Research & Development Center , HyeopRyeok Road, Siheung-Si, Gyeonggi-do, South Korea.
authors.forename: Jinha
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology , Seoul 136-791, South Korea.
authors.forename: Taslim A
authors.initials: TA
authors.lastname: Al-Hilal
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology , Seoul 136-791, South Korea.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: ST Pharm Research & Development Center , HyeopRyeok Road, Siheung-Si, Gyeonggi-do, South Korea.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Kim
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul 151-742, South Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University , Seoul 151-742, South Korea.
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002793:Cholic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D017984:Enoxaparin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation; D061985:Madin Darby Canine Kidney Cells / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D020246:Venous Thrombosis / Q000188:drug therapy*
chemical_list: D002793:Cholic Acids; D017984:Enoxaparin; C000620286:tetradeoxycholic Acid