Design And Synthesis Of Photoaffinity Labeling Small Molecular Probes Of Maslinic Acid And Their Application

The PAL-CC-ABPP (photoaffinity labeling click chemistry activity-based protein profiling) strategy, which is one of the important stages in drug discovery, utilizes activity-based probes to discover target proteins and research their functions. Maslinic acid (MA) has various pharmacological activities and exhibited inhibition to glycogen phosphorylase (GP) and protein tyrosine phosphatase 1B (PTP1B), which are recognized as for treatment of type-2 diabetes. In this thesis, some photoaffinity labeling small molecular probes of maslinic acid were designed and synthesized.(1) The molecular probeⅠwas designed and synthesized with MA as the active group, trifluoromethylphenyl diazirine as the photoaffinity labeling group, polyethylene glycol as the linker unit, and azidoacetyl as the potent reporter group.(2) The molecular probeⅡwas designed and synthesized with linear alkane, instead of polyethylene glycol in molecular probeⅠ, as the linker unit.(3) The molecular probeⅢwas designed and synthesized with MA as the active group, BODIPY as the reporter group, linear alkane as the linker group, and trifluoromethylphenyl diazirine as the photoaffinity labeling group.All the structures were characterized by 1H-NMR,MS spectroscopy.(4) The preliminary bioassay test showed inhibitory activity on PTP1B, and the IC50 value for molecular probesⅠ,Ⅱ, andⅢwere 13.62μM,2.24μM,2.30μM.The molecular probesⅡ,Ⅲcan be used to identify exact target protein of MA's antidiabetic pharmacological effect. We speculated that maybe MA has some other target sites for it has various pharmacological activities, and the molecular probes would be used to identify new target proteins and promote the related drug discovery. This work is still on going.