Design, Synthesis, and Therapeutic Evaluation of Poly(acrylic acid)鈥搕etraDOCA Conjugate as a Bile Acid Transporter Inhibitor

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• 作者：Jooho Park ; Taslim A. Al-Hilal ; Jee-Heon Jeong ; Jeong uk Choi ; Youngro Byun
• 刊名：Bioconjugate Chemistry
• 出版年：2015
• 出版时间：August 19, 2015
• 年：2015
• 卷：26
• 期：8
• 页码：1597-1605
• 全文大小：550K
• ISSN：1520-4812

文摘

Regulation of cholesterol and bile acid homeostasis has been attracting attention as a pharmaceutical target for the treatment of diseases, such as hypercholesterolaemia and type 2 diabetes. In recent years, small bile acid analogues have been developed for the purpose of apical sodium-dependent bile acid transporter (ASBT) inhibition. Here, we designed a novel hydrophilic ASBT inhibitor using oligomeric bile acid with a high affinity with ASBT. Polyacrylic acid鈥搕etraDOCA conjugates (PATD) have the ability to bind to ASBT in order to induce hypocholesterolemic effects. Both the viability and the functionality of PATD were evaluated in vitro, showing that PATDs were effective in inhibiting the increases of cholesterol in the blood and oil in the liver induced by high fat diet (HFD). The results indicated that the newly developed biomaterials with oligomeric bile acids and a hydrophilic polymer are potent therapeutic agents for hyperlipidemia.