A new chromogenic and fluorescent ＂turn-on＂ chemodosimeter 3 was designed and synthesized by using a fluoride-sensitive self-immolative linker, in combination with the fluorescent dyes 7-hydroxy-4-trifluoromethyl co...A new chromogenic and fluorescent ＂turn-on＂ chemodosimeter 3 was designed and synthesized by using a fluoride-sensitive self-immolative linker, in combination with the fluorescent dyes 7-hydroxy-4-trifluoromethyl coumarin. The chemodosimeter exhibited high selectivity and sensitivity toward fluoride anions through ＂turn-on＂ chromogenic and fluorogenic dual modes.展开更多
Self-immolative linkers have been widely used to construct prodrugs to improve their efficacy and safety.In this study,we report the use of phenoxysilyl linker as a self-immolative unit to prepare antibody-drug conjug...Self-immolative linkers have been widely used to construct prodrugs to improve their efficacy and safety.In this study,we report the use of phenoxysilyl linker as a self-immolative unit to prepare antibody-drug conjugates(ADCs).Phenoxysily based ADC Ate-PPS-CA4 was prepared and its release was systematically investigated by mass spectrometry.Biological evaluation showed that Ate-PPS-CA4 displayed the ability to target delivery and self-immolative release the active payload CA4 on PD-L1 positive cells MDA-MB-231.As the same with its payload CA4,it could arrest the cell cycle to the G2/M phase and induced changes in cell morphology at the dose of its IC_(50).The development of this linker with novel drug release mechanisms will expand the methodology to construct ADCs,especially for non-internalizing ADCs by extracellular cleavage.展开更多
基金financial support from National Natural Science Foundation of China (No. 21202099)the Science Foundation of Shanghai Institute of Technology (No. YJ2011-75)the Opening Fund of Shanghai Key Laboratory of Chemical Biology (No. SKLCB-2014-01)
文摘A new chromogenic and fluorescent ＂turn-on＂ chemodosimeter 3 was designed and synthesized by using a fluoride-sensitive self-immolative linker, in combination with the fluorescent dyes 7-hydroxy-4-trifluoromethyl coumarin. The chemodosimeter exhibited high selectivity and sensitivity toward fluoride anions through ＂turn-on＂ chromogenic and fluorogenic dual modes.
基金supported by Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at Shanghai Tech University。
文摘Self-immolative linkers have been widely used to construct prodrugs to improve their efficacy and safety.In this study,we report the use of phenoxysilyl linker as a self-immolative unit to prepare antibody-drug conjugates(ADCs).Phenoxysily based ADC Ate-PPS-CA4 was prepared and its release was systematically investigated by mass spectrometry.Biological evaluation showed that Ate-PPS-CA4 displayed the ability to target delivery and self-immolative release the active payload CA4 on PD-L1 positive cells MDA-MB-231.As the same with its payload CA4,it could arrest the cell cycle to the G2/M phase and induced changes in cell morphology at the dose of its IC_(50).The development of this linker with novel drug release mechanisms will expand the methodology to construct ADCs,especially for non-internalizing ADCs by extracellular cleavage.
