Solution-Phase DNA-Compatible Pictet-Spengler Reaction Aided by Machine Learning Building Block Filtering
文献类型:期刊论文
作者 | Li, Ke5; Liu, Xiaohong1,2,3,6; Liu, Sixiu3,4; An, Yulong5; Shen, Yanfang5; Sun, Qingxia5; Shi, Xiaodong5; Su, Wenji5; Cui, Weiren5; Duan, Zhiqiang3,4 |
刊名 | ISCIENCE |
出版日期 | 2020-06-26 |
卷号 | 23期号:6页码:104 |
DOI | 10.1016/j.isci.2020.101142 |
通讯作者 | Zheng, Mingyue(myzheng@simm.ac.cn) ; Peng, Xuanjia(peng_xuanjia@wuxiapptec.com) ; Lu, Xiaojie(xjlu@simm.ac.cn) |
英文摘要 | The application of machine learning toward DNA encoded library (DEL) technology is lacking despite obvious synergy between these two advancing technologies. Herein, a machine learning algorithm has been developed that predicts the conversion rate for the DNA-compatible reaction of a building block with a model DNA-conjugate. We exemplify the value of this technique with a challenging reaction, the Pictet-Spengler, where acidic conditions are normally required to achieve the desired cyclization between tryptophan and aldehydes to provide tryptolines. This is the first demonstration of using a machine learning algorithm to cull potential building blocks prior to their purchase and testing for DNA-encoded library synthesis. Importantly, this allows for a challenging reaction, with an otherwise very low bur block pass rate in the test reaction, to still be used in DEL synthesis. Furthermore, because our protocol is solution phase it is directly applicable to standard plate-based DEL synthesis. |
WOS关键词 | DISCOVERY ; TECHNOLOGY ; CHEMISTRY ; LIBRARIES ; SELECTION ; DESIGN |
资助项目 | National Natural Science Foundation of China[81773634] ; National Natural Science Foundation of China[21877117] ; National Natural Science Foundation of China[91953203] ; National Natural Science Foundation of China[21907105] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-005] ; Chinese Academy of Sciences[XDA12050201] ; Chinese Academy of Sciences[XDA12040330] ; Chinese Academy of Sciences[XDA12050405] ; Shanghai Commission of Science and Technology[18431907100] |
WOS研究方向 | Science & Technology - Other Topics |
语种 | 英语 |
出版者 | CELL PRESS |
WOS记录号 | WOS:000548210600004 |
源URL | [http://119.78.100.183/handle/2S10ELR8/292031] |
专题 | 新药研究国家重点实验室 |
通讯作者 | Zheng, Mingyue; Peng, Xuanjia; Lu, Xiaojie |
作者单位 | 1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd,Zhang Jiang Hitech Pk, Shanghai 201203, Peoples R China 5.WuXi AppTec, DNA Encoded Lib Platform, 288 Fute Zhong Rd, Shanghai 200131, Peoples R China 6.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China |
推荐引用方式 GB/T 7714 | Li, Ke,Liu, Xiaohong,Liu, Sixiu,et al. Solution-Phase DNA-Compatible Pictet-Spengler Reaction Aided by Machine Learning Building Block Filtering[J]. ISCIENCE,2020,23(6):104. |
APA | Li, Ke.,Liu, Xiaohong.,Liu, Sixiu.,An, Yulong.,Shen, Yanfang.,...&Lu, Xiaojie.(2020).Solution-Phase DNA-Compatible Pictet-Spengler Reaction Aided by Machine Learning Building Block Filtering.ISCIENCE,23(6),104. |
MLA | Li, Ke,et al."Solution-Phase DNA-Compatible Pictet-Spengler Reaction Aided by Machine Learning Building Block Filtering".ISCIENCE 23.6(2020):104. |
入库方式: OAI收割
来源:上海药物研究所
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