期刊
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
卷 306, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.saa.2023.123569
关键词
Floxuridine; Transferrin; Catalase; Interaction mechanism
类别
This study investigated the interaction between the anticancer drug FUDR and two important iron-related proteins, BLC and TF. The results showed that FUDR has a strong protective effect in high concentrations and can reduce fluorescence emission intensity through a static mechanism. The binding strength of FUDR with both proteins is similar and mainly involves van der Waals interactions and hydrogen bonds.
In cancer cells that need a lot of iron for growth and metastasis, halo-transferrin (TF-containing iron) enters the cell with the help of the transferrin receptor 1 (TFR1) protein. If the anticancer drug can bind to the iron site by interacting with apo-transferrin (iron-free FT), it can enter the cancer cell by the same mechanism. Two iron related proteins, Bovine liver catalase (BLC) and apo-Transferrin (TF), that are important in cancer patients were selected and their interaction with the anti-cancer drug Floxuridine (FUDR) was investigated. Here, the protective role of FUDR was evaluated by several variables such as drug concentration, interaction time, and temperature-induced degradation of enzyme function. The results showed that the protective effect of the FUDR is greater in high concentrations (in 5 x 10-5 M:1.78 % and 2.59 % after 24 and 48 h). The interaction of the FUDR with both proteins can reduce the intensity of the fluorescence emission by a static mechanism. The binding strength of the FUDR with both proteins was almost similar and with the order of 104 M-1 (Kb = 3.90 +/- 0.41 x 104 M-1 for BLC-FUDR and 5.01 +/- 0.36 x 104 M-1 for TF-FUDR at 310 K). The thermodynamic calculations (in agreement with the docking results) indicated that FUDR-protein complex formation was exothermic and the main binding forces in the binding process were van der Waals interactions and hydrogen bonds. Both fluorophores tryptophan (Trp) and tyrosine (Tyr) of both proteins had significant roles in fluorescence quenching and the interaction process, the polarity of their microenvironment changed. CD results showed that the secondary structure changes of TF are slightly more than BLC. Molecular docking showed that the binding of the FUDR to TF is very close to the Fe-specific site and is placed in the cavity among the wrapping domain, N-Terminal arm, and beta-barrel in BLC.
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