Parallel screening and cheminformatics modeling of flavonoid activated aptasensors  

作　　者：Yu Xiu Ni Zhang Pranesha Prabhakaran Sungho Jang Qipeng Yuan Curt MBreneman Gyoo Yeol Jung Wanwipa Vongsangnak Mattheos A.G.Koffas 

机构地区：[1]Beijing Key Laboratory of Bioactive Substances and Functional Food,Beijing Union University,Beijing,100029,China [2]Department of Chemical and Biological Engineering,Center for Biotechnology and Interdisciplinary Studies,Rensselaer Polytechnic Institute,Troy,NY,12180,USA [3]State Key Laboratory of Chemical Resource Engineering,Beijing University of Chemical Technology,Beijing,100029,China [4]Department of Chemistry and Chemical Biology,Rensselaer Polytechnic Institute,Troy,NY,12180,USA [5]Interdisciplinary Graduate Programs in Bioscience,Faculty of Science,Kasetsart University,Bangkok,10900,Thailand [6]Omics Center for Agriculture,Bioresources,Food,and Health,Kasetsart University(OmiKU),Bangkok,Thailand [7]Division of Bioengineering,College of Life Sciences and Bioengineering,Incheon National University,119 Academy-ro,Yeonsu-gu,Incheon,22012,South Korea [8]Department of Bioengineering and Nano-Bioengineering,Incheon National University,119 Academy-ro,Yeonsu-gu,Incheon,22012,South Korea [9]Research Center for Bio Materials&Process Development,Incheon National University,119 Academy-ro,Yeonsu-gu,Incheon,22012,South Korea [10]Department of Chemical Engineering,Pohang University of Science and Technology,77 Cheongam-ro,Nam-gu,Pohang,Gyeongbuk,37673,South Korea [11]School of Interdisciplinary Bioscience and Bioengineering,Pohang University of Science and Technology,77 Cheongam-ro,Nam-gu,Pohang,Gyeongbuk,37673,South Korea [12]Department of Zoology,Faculty of Science,Kasetsart University,Bangkok,10900,Thailand

出　　处：《Synthetic and Systems Biotechnology》2022年第4期1148-1158,共11页合成和系统生物技术（英文）

基　　金：This work was supported by the Global Research Laboratory Program(NRF 2016K1A1A2912829)through the National Research Foundation of Korea(NRF);This work was also supported by the National Natural Science Foundation of China(grant number 21636001);Research Program of Beijing Municipal Education Commission(grant number KM201911417012);This work was also financially supported by the Office of the Ministry of Higher Education,Science,Research and Innovation;the Thailand Science Research and Innovation through the Kasetsart University Reinventing University Program 2021 and Department of Zoology,Faculty of Science,Kasetsart University;P.P.would like to acknowledge the supports provided by the International Affairs under the scholarship program of ASEAN+6 and Interdisciplinary Graduate Program in Bioscience in Kasetsart University.

摘　　要：A parallel screening of 27 different flavonoids and chalcones was conducted using 6 artificial naringenin-activated riboswitches(M1,M2,M3,O,L and H).A quantitative structure-property relationship approach was applied to understand the physicochemical properties of the flavonoid structures resulting in specificity differences relied on the fluorescence intensity of a green fluorescent protein reporter.Robust models of riboswitches M1,M2 and O that had good predictive power were constructed with descriptors selected for their high correlation.Increased electronegativity and hydrophilicity of the flavonoids structures were identified as two properties that increased binding affinity to RNA riboswitches.Hydroxyl groups at the C-3′and C-4’positions of the flavonoid molecule were strictly required for ligand-activation with riboswitches M1 and M2.Riboswitches O and L preferred multi-hydroxylated flavones as ligands.Substitutions on the A ring of the flavonoid molecule were not important in the molecular recognition process.O-glycosylated derivatives were not recognized by any of the riboswitches,presumably due to steric hindrances.Despite the challenges of detecting RNA conformational change after ligand binding,the resulting models elucidate important physicochemical features in the ligands for conformational structural studies of artificial aptamer complexes and for design of ligands having higher binding specificity.

关 键 词：RIBOSWITCH RNA device FLAVONOIDS Structure-property relationships Physicochemical properties 

分 类 号：O62[理学—有机化学]