Spectroscopic studies of the interaction mechanisms between mono-caffeoylquinic acids and transferrin.
Transferrin (Tf) is an important protein responsible for circulating and transporting iron into cytoplasm. Tf can be taken into cells through endocytosis mediated by Tf receptor, which usually overexpresses in cancer cells. The Tf-Tf receptor pathway opens a possible avenue for novel targeted cancer therapy by utilizing Tf-binding active compounds. Among which, anti-cancer active caffeoylquinic acids (CQAs) were recently found to be promising Tf-binders by our group. For better understanding the anti-cancer activities of CQAs, it is important to unveil the binding mechanisms between CQAs and Tf. In this study, the fluorescence quenching, surface plasmon resonance (SPR), circular dichroism (CD) and molecular docking were used to investigate the interactions between CQA and Tf. The results showed that the calculated apparent association constants of interactions between 1-, 3-, 4- and 5-CQA and Tf at 298K were 7.97×105M-1, 4.36×107M-1, 6.58×105M-1and 4.42×106M-1, respectively. The thermodynamic parameters indicated that the interaction between 1-, 3-, 5-CQA and Tf is due to H-bonding, and electrostatic interactions were likely involved in the binding of 4-CQA and Tf. The CD results indicated that bindings of 1-CQA, 4-CQA and 5-CQA with Tf resulted in more stretched β-turn and random coil translated from β-sheet. In contrast, 3-CQA led to more stable a-helix conformation. Molecular docking studies of CQAs with Tf further displayed that CQAs were able to interact with residues near Fe3+binding site. The spectroscopic studies revealed the action mechanisms, thermodynamics and interacting forces between CQAs and Tf, and thus are helpful for future design and discovery of Tf-binders for targeted cancer therapy applying Tf-Tf receptor pathway.
School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Yanqing
Y
Guan
Shimadzu International Trading (Shanghai) Co. Limited, Beijing 100020, China.
Jing
J
Dong
School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Shizhong
S
Chen
School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Meixian
M
Liu
School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Daidong
D
Wang
School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Xiaotian
X
Zhang
School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: hw9505@bjmu.edu.cn.
Hong
H
Wang
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, United States. Electronic address: zlin8@uthsc.edu.
Zongtao
Z
Lin
D002942:Circular Dichroism; D006801:Humans; D016014:Linear Models; D062105:Molecular Docking Simulation; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance; D013816:Thermodynamics; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism*
D014168:Transferrin; C472707:caffeoylquinic acid; D011801:Quinic Acid
Caffeoylquinic acids; Circular dichroism; Fluorescence quenching; Molecular docking; Surface plasmon resonance; Transferrin