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 ...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.展开更多
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)+3 种基金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 Innovationthe Thailand Science Research and Innovation through the Kasetsart University Reinventing University Program 2021 and Department of Zoology,Faculty of Science,Kasetsart UniversityP.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.
文摘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.
