Interaction between a novel folate receptor targeted rhaponticin conjugate and human serum albumin by molecular spectroscopy / 国际药学研究杂志

ABSTRACT

Objective To investigate the affinity and interaction of a folate receptor targeted rhapontion(RHA)conjugate (FRHA)with human serum albumins(HSA). Method The interaction between FRHA and HSA under physiological conditions was investigated by fluorescence spectroscopy,UV-visual(vis)spectroscopy and circular dichroism(CD)spectroscopy. Great attempts were made to investigate their interaction mechanism regarding the quenching mechanism,the specific binding site,the type of inter-action force,and the effect of FRHA on the micro-environmental and conformational changes in HSA molecules. Results The forma-tion of the complex of FRHA-HSA would lead to fluorescence quenching. The corresponding values of Ka were 1.4322 × 105,1.1793 × 105,0.9334 × 105 and 0.7896 × 105 L/mol when the temperature were 298,302,306,and 310 K,respectively. The enthalpy change (ΔH)and entropy change(ΔS)were calculated to be-38.772 kJ/mol and-31.39 J/(mol·K),indicating that van der Waals force and hydrogen bonds played major roles in stabilizing the complex. Conclusion The interaction process of the formation of FRHA-HSA is spontaneous. The negative values of enthalpy change(ΔH)and entropy change(ΔS)indicate that van der Waals force and hydrogen bonds play major roles in stabilizing the complex. The conformational investigation reveals theα-helical structure is decreased and the microenvironment of HSA is changed upon the addition of FRHA. The fluorescence quenching of HSA caused by FRHA is static quenching. Furthermore,the results of site marker competitive experiment suggest that FRHA binds to the sub-domainⅡA of HSA.