基本介紹
- 中文名：於日磊
- 學位/學歷：博士
- 職業：教師
- 專業方向：螺毒素的結構最佳化
- 任職院校：中國海洋大學
個人經歷,研究方向,學術成果,
個人經歷
2009年6月到2013年1月在澳大利亞昆士蘭大學（University of Queensland）著名多肽藥物領域David Craik教授課題組學習，從事芋螺毒素結構藥效學研究，獲藥物化學博士學位。2013年3月到2014年9月，在牛津大學生物化學系Prof. Philip Biggin課題組從事計算機藥物設計與膜蛋白受體的分子動力學模擬的博士後研究。2014年10月起，經中國海洋大學“青年英才工程”人才引進在中國海洋大學醫藥學院工作。
研究方向
（1）芋螺毒素的結構最佳化、化學修飾與作用機制的研究：α芋螺毒素選擇性作用於乙醯膽鹼受體，主要採用計算機模擬、固定相多肽合成、核磁共振等技術對芋螺毒素的結構進行改造與化學修飾以提高它的活性、穩定性與選擇性 ；（2）抗腫瘤環肽的設計：自然界存在具有抗腫瘤活性多肽片段，它們的穩定性差，容易被降解，主要採用多肽嫁接技術，把具有抗腫瘤活性的多肽片段嫁接到已知具有穩定結構的環肽中，以提高它的穩定性、生物利用度與抗腫瘤活性；（3）計算機藥物設計與膜蛋白受體的分子動力學模擬。
學術成果
近5年在JBC、Scientific Reports、Plos Comput Bio、J Med Chem、Nuclear acids Research、J Chem Inf Model, J Physical Chem B、Biophysical J、Biochemistry等雜誌發表SCI論文29餘篇。現主持國家自然基金、中央高校建設基金、青島市專項、博士後基金等6項。
科研項目
1.具有新穎二硫鍵骨架的環α型芋螺毒素類似物的設計與構效學研究。國家青年科學基金項目（81502977），21.48萬元，2016.01~2018.12（項目負責人）
2.中國海洋大學“青年英才工程”項目，10萬元，2014.11~2017.11（項目負責人）。
3.中央高校基本業務經費，60萬， 2017~2020 （項目負責人）
4.青島市青年基礎專項， 5萬， 2015~2017 （項目負責人）
發表文章 （* 通訊作者）：
(1) Nargis Tabassum, Han-Shen Tae, Xinying Jia, Quentin Kaas, Tao Jiang, David J. Adams,
and Rilei Yu*, Role of Cys I –Cys III Disulfide Bond on the Structure and Activity of α-Conotoxins at Human Neuronal Nicotinic Acetylcholine Receptors. ACS Omega. 2017, 2, 4621−4631. DOI: 10.1021/acsomega.7b00639
(2) Tabassum N, Ma Q, Wu G, Jiang T, Yu R*. Exploring the binding energy profiles of full agonists, partial agonists, and antagonists of the α7 nicotinic acetylcholine receptor.J Mol Model. 2017 Sep;23(9):251. doi: 10.1007/s00894-017-3419-4. Epub 2017 Aug 2.
(3) Ma Q, Tae HS, Wu G, Jiang T, Yu R*. Exploring the Relationship between Nicotinic Acetylcholine Receptor Ligand Size, Efficiency, Efficacy, and C-Loop Opening.J Chem Inf Model. 2017 Aug 28;57(8):1947-1956. doi: 10.1021/acs.jcim.7b00152. Epub 2017 Aug 2
(4) Jiang, L.; Yin, R.; Wang, X.; Dai, J.; Li, J.; Jiang, T*.; Yu, R*. Design and Synthesis of Neolamellarin a Derivatives Targeting Heat Shock Protein 90. Eur. J. Med. Chem. 2017, 135, 24–33.
(5) Ming-Jing Li Guan-Zhao Wu Quentin Kaas [...] Rilei Yu* Development of Efficient Docking Strategies and Structure-activity Relationship Study of the c-Met Type II Inhibitors. Journal of molecular graphics & modelling. 2017
(6) Lan-Ting XinLu LiuChang-Lun Rilei Yu Shao Chang-Yun Wang* Discovery of DNA Topoisomerase I Inhibitors with Low-Cytotoxicity Based on Virtual Screening from Natural Products. Marine Drugs.
(7) Cuny H, Yu R, Tae HS, Kompella SN, Adams DJ. α-Conotoxins active at α3-containing nicotinic acetylcholine receptors and their molecular determinants for selective inhibition. Br J Pharmacol. 2017 May 6. doi: 10.1111/bph.13852. [Epub ahead of print] Review.
(8) Safar, F.; Hurdiss, E.; Erotocritou, M.; Greiner, T.; Lape, R.; Irvine, M. W.; Fang, G.; Jane, D.;Yu, R.; Dämgen, M. A.; Biggin, P. C.; Sivilotti, L. G*. The Startle Disease Mutation E103K Impairs Activation of Human Homomeric α1 Glycine Receptors by Disrupting an Intersubunit Salt Bridge across the Agonist Binding Site. J. Biol. Chem. 2017.
(9) Wang, W.; Yin, R.; Zhang, M.; Yu, R.; Hao, C.; Zhang, L.; Jiang, T. Boronic Acid Modifications Enhance the Anti-Influenza A Virus Activities of Novel Quindoline Derivatives. J. Med. Chem. 2017, 60 (7), 2840–2852.
(10) Zhang, R.; Yu, R.; Xu, Q.; Li, X.; Luo, J.; Jiang, B.; Wang, L.; Guo, S.; Wu, N.; Shi, D. Discovery and Evaluation of the Hybrid of Bromophenol and Saccharide as Potent and Selective Protein Tyrosine Phosphatase 1B Inhibitors. Eur. J. Med. Chem. 2017, 134, 24–33.
(11) Tabassum N.,Yu R*.,Jiang T*. Computational determination of the binding mode of α-conotoxin to nicotinic acetylcholine receptor. Journal of Ocean University of China. 2016, 15(6):1027-1033
(12) Braun, N.; Lynagh, T.; Yu, R.; Biggin, P. C.; Pless, S. A. Role of an Absolutely Conserved Tryptophan Pair in the Extracellular Domain of Cys-Loop Receptors. ACS Chem. Neurosci.2016.
(13) Cuny, H.; Kompella, S. N.; Tae, H.-S.; Yu, R.; Adams, D. J. Key Structural Determinants in the Agonist Binding Loops of Human β2 and β4 Nicotinic Acetylcholine Receptor Subunits Contribute to α3β4 Subtype Selectivity of α-Conotoxins. J. Biol. Chem.2016, 291 (45), 23779–23792.
(14) Liu, M.; Chen, F.; Yu, R.; Zhang, W.; Han, M.; Liu, F.; Wu, J.; Zhao, X.; Miao, J. Synthesis and Cytotoxicity against K562 Cells of 3-O-Angeloyl-20-O-Acetyl Ingenol, a Derivative of Ingenol Mebutate. Int. J. Mol. Sci.2016, 17 (8).
(15) Tong, S.; Zhang, M.; Wang, S.; Yin, R.; Yu, R.; Wan, S.; Jiang, T.; Zhang, L. Isothiouronium Modification Empowers Pyrimidine-Substituted Curcumin Analogs Potent Cytotoxicity and Golgi Localization. Eur. J. Med. Chem.2016, 123, 849–857.
(16) Yu, Z.; Sun, W.; Peng, W.; Yu, R.; Li, G.; Jiang, T. Pharmacokinetics in Vitro and in Vivo of Two Novel Prodrugs of Oleanolic Acid in Rats and Its Hepatoprotective Effects against Liver Injury Induced by CCl4.Mol. Pharm.2016, 13 (5), 1699–1710.
(17) Yu, R.; Tabassum, N.; Jiang, T. Investigation of α-Conotoxin Unbinding Using Umbrella Sampling. Bioorg. Med. Chem. Lett.2016
(18) Zhang, R.; Chen, S.; Wang, X.; Yu, R.; Li, M.; Ren, S.; Jiang, T. Synthesis and DNA-Binding Properties of Novel DNA Cyclo-Intercalators Containing Purine-Glucuronic Acid Hybrids. Carbohydr. Res.2016, 42
(19) Yu, R.; Seymour, V. A. L.; Berecki, G.; Jia, X.; Akcan, M.; Adams, D. J.; Kaas, Q.; Craik, D. J. Less Is More: Design of a Highly Stable Disulfide-Deleted Mutant of Analgesic Cyclic α-Conotoxin Vc1.1. Sci. Rep.2015, 5, 13264.
(20) Kang, C.; Liu, D.; Wang, X.; Yu, R.; Lv, Y. The Unbinding Studies of Vascular Endothelial Growth Factor Receptor-2 Protein Tyrosine Kinase Type II Inhibitors. J. Mol. Graph. Model.2015, 59, 130–135.
(21) Liu, S.; Wang, W.; Jiang, L.; Wan, S.; Zhang, L.; Yu, R.; Jiang, T. 2-Pyridinyl-4(3H)-Quinazolinone: A Scaffold for Anti-Influenza A Virus Compounds. Chem. Biol. Drug Des.2015, n/a – n/a.
(22) Greiner, T.; Hurdiss, E.; Yu, R.; Lape, R.; Biggin, P. C.; Sivilotti, L. G. Interaction of the Glycine Receptor Alpha 1 Binding Site with Partial Agonists.Biophys. J.2014, 106 (2), 547a.
(23) Shao, S.; Yu, R.; Yu, Y.; Li, Y. Dual-Inhibitors of STAT5 and STAT3: Studies from Molecular Docking and Molecular Dynamics Simulations. J. Mol. Model.2014, 20 (8), 2399.
(24) Yu, R.; Hurdiss, E.; Greiner, T.; Lape, R.; Sivilotti, L.; Biggin, P. C. Agonist and Antagonist Binding in Human Glycine Receptors. Biochemistry (Mosc.)2014, 53 (38), 6041–6051.
(25) Yu, R.; Kompella, S. N.; Adams, D. J.; Craik, D. J.; Kaas, Q. Determination of the α-Conotoxin Vc1.1 Binding Site on the α9α10 Nicotinic Acetylcholine Receptor. J. Med. Chem.2013, 56 (9), 3557–3567.
(26) Shi, C.; Yu, R.; Shao, S.; Li, Y. Partial Activation of α7 Nicotinic Acetylcholine Receptors: Insights from Molecular Dynamics Simulations. J. Mol. Model.2013, 19 (2), 871–878.
(27) Yu, R.; Kaas, Q.; Craik, D. J. Delineation of the Unbinding Pathway of α-Conotoxin ImI from the α7 Nicotinic Acetylcholine Receptor. J. Phys. Chem. B 2012, 116 (21), 6097–6105.
(28) Kaas, Q.; Yu, R.; Jin, A.-H.; Dutertre, S.; Craik, D. J. ConoServer: Updated Content, Knowledge, and Discovery Tools in the Conopeptide Database. Nucleic Acids Res.2012, 40 (Database issue), D325–D330.
(29) Yu, R.; Craik, D. J.; Kaas, Q. Blockade of Neuronal α7-nAChR by α-Conotoxin ImI Explained by Computational Scanning and Energy Calculations.PLoS Comput. Biol.2011, 7 (3), e1002011.
