Biomechanical Study Of Organelle Response Ratio Fluorescent Probe And Synthesis Of Non-natural Sialic Acid

pH is closely related to life activities.Lysosomal pH is characterized by dynamic changes in various life processes.The development of a sensitive analytical technique for sensitive analysis of pH dynamics,biomechanically compatible imaging techniques is of great value for lysosomal related signaling and pathology studies.In this paper,a double fluorescence ratio probe(CM-ROX)was synthesized and its fluorescence ratio varied up to 70 times in the range of pH 4.5-6.0.Use of the probe can effectively distinguish the different stress state lysosomal acidity of the dynamic changes(such as autophagy,apoptosis).The fluorescent properties of the probe are compatible with flow cytometry,which makes it easy to quickly analyze the subtle changes in lysosomal acidity.Mitochondrial membrane potential(??m)is one of the core features of mitochondria.??m reduction is an important precursor of apoptosis.Sensitive dynamic monitoring of ??m changes is important for the study of mitochondrial function.This thesis designed a double organelle response ratio of fluorescent probe RC-TPP.The probe contains a triphenyl quaternary phosphonium(TPP)functional group for targeting mitochondria.The RC-TPP ratio signal changes significantly at different pH levels.When the mitochondria ??m are lost under external conditions,the probe enters the lysosome and emits red fluorescence by lysosomal acidity activation.The probe was used to elucidate the dynamic association of mitochondrial ATm loss and lysosomal membrane permeability in the process of apoptosis or necrosis.This probe provides a method for the analysis of mitochondrial function and the interaction of mitochondria with lysosomes in subsequent studies.Cell membrane protein and phospholipid are often glycosylated,the layer of glycoconjugate called calyx,calyx on cells and matrix,foreign material binding,identification and response plays an important role.Sialic acid is generally at the end of the calyx,involved in regulating the interaction of cells with the outside world.In this thesis,three kinds of C-9 modified non-natural sialic acid synthesis methods were explored,and 30 non-natural sialic acid derivatives were synthesized.In the future,these non-natural sialic acids will be introduced on tumor calyx for different biomedical research and applications.