Comparison of the interaction between lactoferrin and isomeric drugs

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Molecular and biomolecular spectroscopy, 2017-02, Vol.173, p.593-607
• Main Authors: Guo, Ming, Lu, Xiaowang, Wang, Yan, Brodelius, Peter E.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biokemi; Bovine lactoferrin; Interaction; Oleanolic acid; Ursolic acid
• ISSN: 1386-1425; 1873-3557
• DOI: 10.1016/j.saa.2016.10.029

The binding properties of pentacyclic triterpenoid isomeric drugs, i.e. ursolic acid (UA) and oleanolic acid (OA), to bovine lactoferrin (BLF) have been studied by molecule modeling, fluorescence spectroscopy, UV–visible absorbance spectroscopy and infrared spectroscopy (IR). Molecular docking, performed to reveal the possible binding mode or mechanism, suggested that hydrophobic interaction and hydrogen bonding play important roles to stabilize the complex. The results of spectroscopic measurements showed that the two isomeric drugs both strongly quenched the intrinsic fluorescence of BLF through a static quenching procedure although some differences between UA and OA binding strength and non-radiation energy transfer occurred within the molecules. The number of binding sites was 3.44 and 3.10 for UA and OA, respectively, and the efficiency of Förster energy transfer provided a distance of 0.77 and 1.21nm for UA and OA, respectively. The conformation transformation of BLF affected by the drugs conformed to the “all-or-none” pattern. In addition, the changes of the ratios of α-helices, β-sheets and β-turns of BLF during the process of the interaction were obtained. The results of the experiments in combination with the calculations showed that there are two modes of pentacyclic triterpenoid binding to BLF instead of one binding mode only governed by the principle of the lowest bonding energy. The results of integrating the spectroscopic and molecular docking studies showed that there are two patterns of pentacyclic triterpenoid binding to bovine lactoferrin instead of one binding mode only governed by the principle of lowest bonding energy. [Display omitted] •The interaction between isomeric drugs and proteins was characterized with spectroscopic methods and molecular modeling.•The binding pattern between bovine lactoferrin and isomeric drugs (OA and UA) has been fully characterized.•Differences in the structure of the isomeric drugs lead to different mechanisms of the binding to lactoferrin.•The binding parameters of this new kind of interaction have been determined.