Spectroscopic Investigate The Interaction Between FTO Proteins And Small Molecular Structure Analogs

At present,there are at least 400 million overweight people in China,and obese people account for more than 40%of the national population.At present,overweight and obesity have become a global"epidemic",spreading in both developed countries and developing countries.Research shows that global obesity is not only related to appetite and exercise level,genes are also an important factor in obesity.Researchers for the first time in 2007 found that genes associated with obesity,the FTO gene FTO gene in human skeletal muscle and fat tissue such as hypothalamus are expressed,can adjust the body's metabolism in human body fat,studies have shown that FTO expression may cause or increase the incidence of some cancer and metabolic disease,small molecules can be designed synthetic drugs targeting inhibition of FTO expression.Therefore,the FTO gene and its small molecule inhibitors has become a hot spot in the field of chemistry,biology,pharmaceutical science and related fields.In this paper,molecular docking and spectroscopic methods were used to study the interactions between flavonoid analogues,3-phenyl-[1,2,4]thiadiazole derivatives,benzimidazole and 4-?3H?-quinazolone derivatives,indazole and pyrazole analogues and FTO proteins.The research contents were mainly divided into the following parts:The chapter one mainly introduced the structure and function of FTO protein,the research methods,contents and significance of the interaction between small molecules and protein.The chapter two using molecular docking to predict the interaction between six flavonoid analogues and FTO,the mechanism of six flavonoid analogues and FTO protein was studied by spectrophotometry and isothermal titration calorimetry.The results showed that there was static quenching between flavonoids and FTO protein,flavonoids interacting with amino acid residues of the FTO protein,the activity of3-hydroxyl group was better than that of 5-hydroxyl group,and steric hindrance would affect the binding ability of flavonoid analogues to FTO.The effects of Fe³⁺on the binding of flavonoid analogues to FTO were also investigated.The experimental results showed that the binding ability between six flavonoid analogues and FTO protein was changed by adding Fe³⁺,but the quenching mechanism and force type of the system were not changed.The chapter three using spectroscopy and molecular docking method to research the interaction between 3-phenyl-[1,2,4]thiadiazole derivatives and FTO protein interactions.The results showed that 3-phenyl-[1,2,4]thiadiazole derivatives weaken the intrinsic fluorescence intensity of FTO protein by static quenching,and the amino group of thiadiazole derivative affects 3-phenyl-[1,2,4]thiadiazole derivatives Interaction with the FTO.In chapter four,the interactions of seven indazole and pyrazole analogues with FTO proteins were investigated by spectroscopic and molecular docking methods.The results showed that seven indazole and pyrazole analogues could cause static quenching of FTO endogenous fluorescence and interact with FTO,hydrophobic force was the main force.In chapter five,the interaction of seventeen benzimidazo[1,3,5]triazine derivatives with FTO proteins was studied by spectroscopy and molecular docking.The results showed that the quenching mechanism of seventeen small molecule analogues and FTO was static quenching,all of which could bind to FTO,The activity of compounds containing furan ring was better than that of compounds containing pyridine ring and benzene ring,and the activity of compounds containing ortho-substituents was better than that of isomers containing ortho-substituents.In chapter six,the interaction of seventeen benzimidazoles and3H-4-quinazolinone analogues with FTO proteins was investigated by spectroscopy and molecular docking.The results showed that seventeen structural analogs could statically quench the FTO protein fluorescence,and the phenyl activity was better than the sulphonyl group.