Solution-Phase DNA-Compatible Pictet-Spengler Reaction Aided by Machine Learning Building Block Filtering

doi:10.1016/j.isci.2020.101142

	Solution-Phase DNA-Compatible Pictet-Spengler Reaction Aided by Machine Learning Building Block Filtering
	Li, Ke 2; Liu, Xiaohong3,4,5,6 ; Liu, Sixiu 1,6; An, Yulong 2; Shen, Yanfang 2; Sun, Qingxia 2; Shi, Xiaodong 2; Su, Wenji 2; Cui, Weiren 2; Duan, Zhiqiang 1,6; Kuai, Letian 2; Yang, Hongfang 2; Satz, Alexander L.2; Chen, Kaixian3,4,5,6 ; Jiang, Hualiang3,4,5,6 ; Zheng, Mingyue 5,6; Peng, Xuanjia 2; Lu, Xiaojie 1,6
	2020-06-26
发表期刊	ISCIENCE (IF:4.6[JCR-2023],5.0[5-Year])
EISSN	2589-0042
卷号	23 期号:6
发表状态	已发表
DOI	10.1016/j.isci.2020.101142
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.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China[81773634][21877117][91953203][21907105] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program," China[2018ZX09711002][2018ZX09711002-005] ; Chinese Academy of Sciences[XDA12050201][XDA12040330][XDA12050405] ; Shanghai Commission of Science and Technology[18431907100]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000548210600004
出版者	CELL PRESS
WOS关键词	DISCOVERY ; TECHNOLOGY ; CHEMISTRY ; LIBRARIES ; SELECTION ; DESIGN
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/122481
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_陈凯先组免疫化学研究所_特聘教授组_蒋华良组
通讯作者	Zheng, Mingyue; Peng, Xuanjia; Lu, Xiaojie
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd,Zhang Jiang Hitech Pk, Shanghai 201203, Peoples R China 2.WuXi AppTec, DNA Encoded Lib Platform, 288 Fute Zhong Rd, Shanghai 200131, Peoples R China 3.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 6.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, 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).
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).
MLA	Li, Ke,et al."Solution-Phase DNA-Compatible Pictet-Spengler Reaction Aided by Machine Learning Building Block Filtering".ISCIENCE 23.6(2020).