The effect of the skeleton structure of flavanone and flavonoid on interaction with transferrin.
Transferrin has been exploited as a potential drug carrier for targeted drug delivery into cancer cells, which express high levels of transferrin receptors. In the present study, we identified specific structural features in flavonoids that were critical for binding to transferrin. Flavanone naringenin and flavonoid apigenin, two flavonoids with characteristic flavonoid core structures were selected for the study of the effects of C2-C3 single bond in the C-ring on transferrin binding. We determined the binding affinities by fluorescence quenching experiments and investigated the binding modes by CD spectra and molecular modeling. Our results demonstrated that naringenin bound transferrin with an affinity almost 100 times higher than that of apigenin attributed to its higher structural flexibility and lower acidity compared with apigenin. Our docking study showed that naringenin had stronger van der Waals interactions with transferrin, which was believed to contribute to its higher binding affinity. We also found that naringenin-binding induced greater increase in the α-helix content in transferrin than apigenin, suggesting that transferrin became more compact upon association with naringenin. Our study demonstrated that naringenin was a ligand for transferrin with good affinity. The results reported herein can facilitate the design and development of drugs that bind transferrin with high affinity.
College of Chemical Engineering, Hebei United University, Tangshan, Hebei 063009, China. Electronic address: zhangxf@heuu.edu.cn.
Xiu-feng
XF
Zhang
Rui-min
RM
Han
Xiao-ran
XR
Sun
Guang-yue
GY
Li
Qian-fan
QF
Yang
Qian
Q
Li
Wei
W
Gai
Miao
M
Zhang
Lei
L
Chen
Guang
G
Yang
Ya-lin
YL
Tang
D047310:Apigenin / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002942:Circular Dichroism; D044950:Flavanones / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*
D044950:Flavanones; D014168:Transferrin; D047310:Apigenin; C005273:naringenin
Apigenin; CD; Fluorescent quenching; Naringenin; Tansferrin