Identification of the binding between three fluoronucleoside analogues and fat mass and obesity-associated protein by isothermal titration calorimetry and spectroscopic techniques
The characteristics of the interactions between FTO and fluoronucleoside analogs were investigated by ITC and spectral methods.
In this work, the interactions between fat mass and obesity-associated (FTO) protein and three fluoronucleoside analogues (three-member-ring compound (1a), five-member-ring compound (1b) and six-member-ring compound (1c)) have been investigated by fluorescence, ultraviolet-visible absorption spectroscopy, isothermal titration calorimetric (ITC) and molecular modeling. Analysis of fluorescence data showed that the binding between three analogues and FTO occurred via a static quenching mechanism. Both ITC and fluorescence results indicated that 1b is the strongest quencher. In contrast to spectroscopy techniques, ITC results suggested that there is no binding for 1c. ITC results showed that the binding between FTO and 1a (or 1b) were exothermic. Fluorescence results showed that the binding between three analogues and FTO were endothermic. Results of thermodynamic analysis and molecular modeling suggested that it was entropy driven event between FTO and 1a (or 1b).