Park, Jooho Jeon, Ok Cheol Yun, Jisuk Nam, Hwajung Hwang, Jinha Al-Hilal, Taslim A. Kim, Kwangmeyung Kim, Kyungjin Byun, Youngro 2024-01-20T02:34:06Z 2024-01-20T02:34:06Z 2022-01-25 2016-12 0022-2623 https://pubs.kist.re.kr/handle/201004/123341 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. English AMER CHEMICAL SOC End-Site-Specific Conjugation of Enoxaparin and Tetradeoxycholic Acid Using Nonenzymatic Glycosylation for Oral Delivery Article 10.1021/acs.jmedchem.6b00936 1 JOURNAL OF MEDICINAL CHEMISTRY, v.59, no.23, pp.10520 - 10529 JOURNAL OF MEDICINAL CHEMISTRY 59 23 10520 10529 N scie scopus 000389623900010 2-s2.0-85003632913 Chemistry, Medicinal Pharmacology & Pharmacy Article MOLECULAR-WEIGHT HEPARIN DEEP-VEIN THROMBOSIS DEOXYCHOLIC-ACID CHEMICAL GLYCOSYLATION VENOUS THROMBOEMBOLISM ANTICOAGULANT PREVENTION MECHANISM MACROMOLECULES PROPHYLAXIS