Design,Synthesis And Application Of Novel Fluorescent Probes For Prolyl Aminopeptidases And Cysteine

There are many molecular detection methods,such as magnetic resonance imaging(MRI),computed tomography(CT)and positron emission tomography(PET)and other classical imaging techniques,but these techniques do not directly and on a real-time scale to monitor many biological phenomena.Recently,fluorescent probes have attracted considerable attention because they can enter the living body in a non-invasive manner and can be optically imaged.Although the fluorescence probe is less sensitive than the radioactive material,it has the advantages of low cost,safety and easy operation compared with MRI,CT and radioactive probe.Prolyl aminopeptidases(PAP)is a specific extracellular peptide enzyme that catalyzes the hydrolysis of the N-end proline residues of peptide and protein.Protein hydrolysis is an important process in the process of meat fermentation,resulting in the production of small peptides and free amino acids.This process affects food taste and safety,which in turn affects human health.PAP plays an important role in protein digestion,apoptosis and cell proliferation,so the detection of proline enzyme(PAP)is of great significance and value to the production and life of human society.We design a well-water-soluble fluorescent probe NIR-PAP.The probe acts on the peptide bond between cysteine and proline after contact with PAP,which makes the peptide bond broken.Then the subsequent molecules have cyclization reaction and the NIR fluorescent dye will be released.The fluorescent group produced by the reaction of the probe and the proline enzyme(PAP)is a high-resolution near-infrared dye based on the semi-flower green,which can emit near-infrared fluorescence signal.So it has the advantages of strong deep tissue penetration ability and minimal photoluminescence damage to biological samples when doing cell imaging experiments.Therefore,probe NIR-PAP can be a favorable tool for real-time detection of proline enzyme(PAP)in organisms.Thiols,such as cysteine(Cys),homocysteine(Hcy)and glutathione(GSH),play a number of vital roles in biological systems.The metabolism and transport of these sulfur-containing compounds in biological systems is related to a range of important enzymes and proteins.The endogenous concentration of these thiol s indicates that the functional state and abnormal level of the corresponding enzymes and proteins are related to the disease.We design a fluorescent off-on probe DCI-Ac based on dicyanoisophorone dye as parent,propenoic acid ester as the reaction point.Under the action of cysteine,the acryl group is removed to expose the hydroxyl group.Due to its strong electron donating ability,it can form a push-pull system with the dicyano group in the dye,resulting in a strong ICT effect.Then the fluorescence will be restored.At the same time,we are going to use the probe for cell imaging.