Chung, Seung Woo Lee, Myungjin Bae, Sang Mun Park, Jooho Jeon, Ok Cheol Lee, Hui Sun Choe, Han Kim, Han Sung Lee, Beom Suk Park, Rang-Woon Kim, Sang Yoon Byun, Youngro 2024-01-20T13:32:01Z 2024-01-20T13:32:01Z 2021-09-04 2012-12 0142-9612 https://pubs.kist.re.kr/handle/201004/128618 Heparin, a potent anticoagulant used for the prevention of venous thromboembolism, has been recognized as a tumor angiogenesis inhibitor. Its limitation in clinical application for cancer therapy, however, arises from its strong anticoagulant activity, which causes associated adverse effects. In this study, we show the structural correlation of LHT7, a previously developed heparin-based angiogenesis inhibitor, with its influence on VEGF blockade and its decreased anticoagulant activity. LHT7 was characterized as having average seven molecules of sodium taurocholates conjugated to one molecule of low-molecular-weight heparin (LMWH). This study showed that the conjugation of sodium taurocholates selectively blocked interaction with antithrombin III (ATIII) while enhancing the binding with VEGF. This resulted in LHT7 to have negligible anticoagulant activity but potent anti-angiogenic activity. Following up on this finding, we showed that the bidirectional effect of sodium taurocholate conjugation was due to its unique structure, that is, the sterane core hindering the ATIII-binding pentasaccharide unit of LMWH with its bulky and rigid structural characteristics while the terminal sulfate group interacts with VEGF to produce stronger binding. In addition, we showed that LHT7 was localized in the tumor, especially on the endothelial cells. One explanation for this might be that LHT7 was delivered to the tumor via platelets. (C) 2012 Elsevier Ltd. All rights reserved. English ELSEVIER SCI LTD MOLECULAR-WEIGHT HEPARIN ENDOTHELIAL GROWTH-FACTOR BINDING SITE MICROCOMPUTED TOMOGRAPHY CANCER SULFATE DERIVATIVES INHIBITOR OPPORTUNITIES BEVACIZUMAB Potentiation of anti-angiogenic activity of heparin by blocking the ATIII-interacting pentasaccharide unit and increasing net anionic charge Article 10.1016/j.biomaterials.2012.09.002 1 BIOMATERIALS, v.33, no.35, pp.9070 - 9079 BIOMATERIALS 33 35 9070 9079 scie scopus 000310721900017 2-s2.0-84867143259 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article MOLECULAR-WEIGHT HEPARIN ENDOTHELIAL GROWTH-FACTOR BINDING SITE MICROCOMPUTED TOMOGRAPHY CANCER SULFATE DERIVATIVES INHIBITOR OPPORTUNITIES BEVACIZUMAB Low-molecular-weight heparin Taurocholate Angiogenesis VEGF Drug design