Title
Studies on the interaction between promethazine and human serum albumin in the presence of flavonoids by spectroscopic and molecular modeling techniques
Author
Ling-Ling He, Zhi-Xin Wang, Yong-Xia Wang, Xian-Ping Liu, Yan-Jie Yang, Yan-Ping Gao, Xin Wang, Bin Liu, Xin Wang
Year
2016
Journal
Colloids and Surfaces B: Biointerfaces
Abstract
Fluorescence, absorption, time-correlated single photon counting (TCSPC), and circular dichroism (CD) spectroscopic techniques as well as molecular modeling method were used to study the binding characterization of promethazine (PMT) to human serum albumin (HSA) and the influence of flavonoids, rutin and baicalin, on their affinity. The results indicated that the fluorescence quenching mechanism of HSA by PMT is a static quenching due to the formation of complex. The reaction was spontaneous and mainly mediated by hydrogen bonds and hydrophobic interactions. The binding distance between the tryptophan residue of HSA and PMT is less than 8 nm, which indicated that the energy transfer from the tryptophan residue of HSA to PMT occurred. The binding site of PMT on HSA was located in sites I and the presence of PMT can cause the conformational changes of HSA. There was the competitive binding to HSA between PMT and flavonoids because of the overlap of binding sites in HSA. The flavonoids could decrease the association constant and increase the binding distance. In addition, their synergistic effect can further change the conformation of HSA. The decrease in the affinities of PMT binding to HSA in the presence of flavonoids may lead to the increase of free drug in blood, which would affect the transportation or disposition of drug and evoke adverse or toxic effect. Hence, rationalising dosage and diet regimens should be taken into account in clinical application of PMT.
Instrument
J-810
Keywords
Circular dichroism, Ligand binding, Secondary structure, Protein folding, Biochemistry