Interaction of Taxol with intravenous immunoglobulin: an inhibition of Taxol from crystallizing in aqueous solution.
The interaction of anti-cancer drug Taxol (paclitaxel) with human intravenous immunoglobulin (IVIG) was studied under simulated physiological conditions in vitro by spectroscopic methods including fluorescence spectra and Fourier transformation infrared (FT-IR) difference spectra. Docking was used to calculate the interaction modes between Taxol with IVIG. Transmission electron microscopy (TEM) experiments were carried out to investigate the formation of aggregate and crystal of Taxol in aqueous solution. The binding parameters were calculated according to the Sips procedure. The Taxol-IVIG complexes showed two types of binding with the average affinity constant of 1.776 x 10(4)+/-1.16 M(-1) (n=2, 296 K) and 0.7386 x 10(4)+/-1.18 M(-1) (n=4, 296 K). The molecules of Taxol were mainly located in CDR of Fab regions and Fc regions of IgG. The interaction of IVIG with Taxol was of non-specific and weak drug-protein binding, and it could inhibit Taxol from crystallizing in aqueous solution when the molar concentration ratio of Taxol to IVIG did not exceed 15:1. The content of secondary structure compositions of free IVIG and its Taxol complexes were calculated by the FT-IR difference spectra with its self-deconvolution, second derivative resolution enhancement and the curve-fitting procedures of amide I band. The observed FT-IR spectral changes indicated a partial unfolding of the protein structure in the presence of Taxol in aqueous solution. IVIG can serve as a transport protein (carrier) for Taxol.
Liu
Yongchun
Y
College of Chemistry and Chemical Engineering, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China.
Yang
Zhengyin
Z
Du
Juan
J
Yao
Xiaojun
X
Zheng
Xudong
X
Lei
Ruixia
R
Liu
Jianning
J
Hu
Huaisheng
H
Li
Hong
H
D003460:Crystallization; D004247:DNA / Q000737:chemistry; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D017239:Paclitaxel / Q000737:chemistry*; D012313:RNA / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry; D012996:Solutions; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared
D016756:Immunoglobulins, Intravenous; D012709:Serum Albumin; D012996:Solutions; D012313:RNA; D004247:DNA; D017239:Paclitaxel