title: Purpurin inhibits adipocyte-derived leucine aminopeptidase and angiogenesis in a zebrafish model.
abstract: Adipocyte-derived leucine aminopeptidase (A-LAP) is a novel member of the M1 family of zinc metallopeptidases, which has been reported to play a crucial role in angiogenesis. In the present study, we conducted a target-based screening of natural products and synthetic chemical libraries using the purified enzyme to search novel inhibitors of A-LAP. Amongst several hits isolated, a natural product purpurin was identified as one of the most potent inhibitors of A-LAP from the screening. In vitro enzymatic analyses demonstrated that purpurin inhibited A-LAP activity in a non-competitive manner with a Ki value of 20 M. In addition, purpurin showed a strong selectivity toward A-LAP versus another member of M1 family of zinc metallopeptidase, aminopeptidase N (APN). In angiogenesis assays, purpurin inhibited the vascular endothelial growth factor (VEGF)-induced invasion and tube formation of human umbilical vein endothelial cells (HUVEC). Moreover, purpurin inhibited in vivo angiogenesis in zebrafish embryo without toxicity. These data demonstrate that purpurin is a novel specific inhibitor of A-LAP and could be developed as a new anti-angiogenic agent.
authors.affiliation: Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Hyomi
authors.initials: H
authors.lastname: Park
authors.affiliation: Faculty of Health Sciences, University of Macau, Av. Universidade, Taipa, Macau Special Administrative Region, China.
authors.forename: Joong Sup
authors.initials: JS
authors.lastname: Shim
authors.affiliation: Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Beom Seok
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutical Engineering, University of Sun Moon, Asansi, Chungnam 336-708, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Department of Genetic Engineering, Kyungpook National University, Puk-Gu, Sankyuk-Dong, 702-701 Daegu, Republic of Korea.
authors.forename: Tae-Lin
authors.initials: TL
authors.lastname: Huh
authors.affiliation: Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Department of Internal Medicine, College of Medicine, Yonsei University, Seoul 120-752, Republic of Korea. Electronic address: kwonhj@yonsei.ac.kr.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D017667:Adipocytes / Q000201:enzymology*; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007931:Leucyl Aminopeptidase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D015027:Zebrafish / Q000502:physiology*
chemical_list: D000880:Anthraquinones; D004791:Enzyme Inhibitors; D007931:Leucyl Aminopeptidase; C511975:purpurin anthraquinone
keywords: Adipocyte-derived leucine aminopeptidase (A-LAP); Angiogenesis; Drug screening; Purpurin