title: Size Controlled Heparin Fragment-Deoxycholic Acid Conjugate Showed Anticancer Property by Inhibiting VEGF165.
abstract: Heparin is a highly sulfated, long, and linear polysaccharide, which can inhibit tumor growth by interacting with growth factors such as bFGF and VEGF. Several researchers have shown the anti-angiogenic effect of heparin and its conjugates in relation to growth factor inhibition. For drug development and inhibition of growth factors using heparin conjugates, the molecular size of heparin may be crucial considering the size of the heparin binding site of growth factors. In this study, we synthesized heparin fragments and deoxycholic acid conjugated heparin fragments (HFD) to search for the optimal size-controlled conjugate that will inhibit the angiogenic effect of VEGF165. We have also shown that the HFDs could have an enhanced therapeutic effect in vitro and in vivo consequent to the molecular size control. HFDs have significant anti-angiogenic effects by blocking the angiogenic activity of VEGF165 depending on its molecular size. Among them, HFD2 was a promising candidate for oral angiogenesis inhibitor. These results suggest that size-controlled synthesis is necessary for heparin-based drug development.
authors.forename: Jooho
authors.initials: J
authors.lastname: Park
authors.affiliation: ‡College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Gyeongbuk South Korea.
authors.forename: Jee-Heon
authors.initials: JH
authors.lastname: Jeong
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.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002236:Carbohydrate Conformation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003840:Deoxycholic Acid / Q000737:chemistry*; D015951:Factor Xa / Q000378:metabolism; D006493:Heparin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008970:Molecular Weight; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D017434:Protein Structure, Tertiary; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003840:Deoxycholic Acid; D006493:Heparin; D015951:Factor Xa