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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2015 > Volume 11 Number 9 > Nam Hee Kim1, Ngoc Bich Pham2, Ronald J. Quinn2, Joong Sup Shim3, Hee Cho1, Sung Min Cho1, Sung Wook Park4, Jeong Hun Kim4, Seung Hyeok Seok5, Jong-Won Oh1, and Ho Jeong Kwon1,6 

The Small Molecule R-(-)-β-O-Methylsynephrine Binds to Nucleoporin 153 kDa and Inhibits Angiogenesis

Nam Hee Kim1, Ngoc Bich Pham2, Ronald J. Quinn2, Joong Sup Shim3, Hee Cho1, Sung Min Cho1, Sung Wook Park4, Jeong Hun Kim4, Seung Hyeok Seok5, Jong-Won Oh1, and Ho Jeong Kwon1,6 
1. Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea 2. Eskitis Institute, Griffith University, Brisbane QLD 4111, Australia 3. Faculty of Health Sciences, University of Macau, Av. Universidade, Taipa, Macau SAR, China 4. Department of Ophthalmology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea 5. Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea 6. Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea  Corresponding author: Ho Jeong Kwon, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. Email: kwonhj@yonsei.ac.kr; Fax: +82 2 362 7265; Tel: +82 2 2123 5883
Abstract :

R-(-)-β-O-methylsynephrine (OMe-Syn) is a naturally occurring small molecule that was identified in a previous screen as an inhibitor of angiogenesis. In this study, we conducted two animal model experiments to investigate the in vivo antiangiogenic activity of OMe-Syn. OMe-Syn significantly inhibited angiogenesis in a transgenic zebrafish model as well as in a mouse retinopathy model. To elucidate the underlying mechanisms responsible for the antiangiogenic activity of OMe-Syn, we used phage display cloning to isolate potential OMe-Syn binding proteins from human cDNA libraries and identified nucleoporin 153 kDa (NUP153) as a primary binding partner of OMe-Syn. OMe-Syn competitively inhibited mRNA binding to the RNA-binding domain of NUP153. Furthermore, depletion of NUP153 in human cells or zebrafish embryos led to an inhibition of angiogenesis, in a manner similar to that seen in response to OMe-Syn treatment. These data suggest that OMe-Syn is a promising candidate for the development of a novel antiangiogenic agent and that inhibition of NUP153 is possibly responsible for the antiangiogenic activity of OMe-Syn

Keywords :
Angiogenesis, Natural product, Small molecule, NUP153, Target identification

Date Deposited : 04 Mar 2016 12:54

Last Modified : 04 Mar 2016 12:54

Official URL: http://www.ijbs.com/v11i9

Volume 11, Number 9, - 2015 , ISSN 1449-2288

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