Study On The Interaction Between Protein With Small Drug And Analogs Molecules By Calorimetry And Spectroscopy

Study on small molecular structure analogues with high molecular protein interactions and for organic compounds in vivo absorption, distribution, metabolism and excretion of process has very important significance, further drug design and development to provide ideas, to screen selected high and low toxicity of a new class of drugs which is always is chemistry, biology, medical science researchers are concerned with the hot.This thesis to human serum albumin(HSA), fat mass and obesity(FTO) as the target protein molecules, in two isomeric, seven oxazole analogues and 11 kinds of nucleoside analogues as the research object, using isothermal titration calorimetry(ITC), m fluorescence spectroscopy and molecular docking technique was used to study the interactions. The results show that :(1) Due to the different position of methyl, G2 and HHb and HSA binding capacity at room temperature is stronger than that of G1; the G1-HSA system, the interaction force was mainly hydrophobic force and electrostatic force; for the G2-HSA system, the hydrophobic force is the main force of Edward and fan interaction, G1-HHb system and the interaction force was mainly hydrophobic force and electrostatic force; for the G2-HHb system, the hydrophobic interaction as the main interaction; all static fluorescence quenching and HSA, HHb; HSA and HHb can cause changes in the molecular conformation,function and HSA fluorescence of amino acid in the role and influence, HHb of tyrosine fluorescence influence of non radiative energy transfer.(2) 11 nucleoside compounds, only compounds YWQ-1f and YWQ-1g and FTO interact with each other, the combination process is the entropy driven based entropy enthalpy driven jointly, the binding force is hydrophobic interactions and hydrogen bonds. YWQ-1g and FTO with stronger ability to YWQ-1f.(3) NPF-6 occurred in the interaction with HSA among 7 kinds of oxazole compounds, occures static fluorescence quenching and HSA, cause HSA molecular conformational changes, combined with the entropy driven process is based on the enthalpy entropy based driven, interactions withhydrophobic interaction. The results of molecular docking and the actual experimental results are consistent.