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Medicinal Chemistry Research

, Volume 26, Issue 12, pp 3286–3295 | Cite as

Interaction of intravenous immunoglobulin and three 20(S)-camptothecin analogs: maintaining higher circulatory levels of the biologically active species

  • Yongchun Liu
  • Yajun Li
  • Xiaojun Yao
  • Yingying Li
  • Huili Qi
  • Kejun Zhang
  • Ruixia Lei
  • Jianning Liu
Original Research
  • 101 Downloads

Abstract

The interaction of intravenous immunoglobulin and three camptothecin analogs, including topotecan, 10-hydroxycamptothecin, 7-ethyl-10-hydroxycamptothecin (SN-38), was studied respectively in vitro. The bindings of intravenous immunoglobulin to these camptothecins were characterized by 2 and/or 4 binding sites with the average affinity constants K o of 103 ~ 104 M−1 at pH 4.0 and 289 ~ 310 K, which were spontaneous, non-specific and weak drug–protein interactions. The observed Fourier transform infrared spectra of intravenous immunoglobulin indicated a partial unfolding of the typical β structure of protein after addition of camptothecins. Based on their distinctive UV–Vis spectra between solutions at pH 4.0, 7.40, and 10.0, the lactone-carboxylate equilibrium of 8.0 μM analogs in pH 7.40 PBS at 310 K in the absence and presence of 2.0 μM intravenous immunoglobulin shifted to the right with the lactone-to-total ratios decreasing from 34.47, 86.68, and 90.40% to 29.76 ~ 32.71%, 56.56 ~ 68.58%, and 86.47 ~ 87.35% for topotecan, 10-hydroxycamptothecin and SN-38, respectively. However, intravenous immunoglobulin could maintain higher circulatory levels of the biologically active species at physiological pH 7.40 in contrast to human serum albumin. Molecular docking was used to calculate the interaction mode and the hydrogen bonding formations were observed between camptothecins and residues of immunoglobulin G. Intravenous immunoglobulin would serve as a transport protein (carrier) for camptothecins.

Keywords

Camptothecin analogs (CPTs) Intravenous immunoglobulin (IVIG) Protein-drug interaction Drug delivery Molecular docking 

Abbreviations

CPT

camptothecin

CPTs

camptothecin analogs

SN-38

7-ethyl-10-hydroxycamptothecin

IVIG

intravenous immunoglobulin

HSA

human serum albumin

FT-IR

fourier transformation infrared

UV-vis

ultraviolet-visible

PBS

phosphate buffered saline

Notes

Funding

The study was supported by Longdong University Doctor Fund (No. XYBY1501, XYBY140210) and Gansu Key Subject Fund of Applied Chemistry (No. GSACKS20130113).

Author contributions

Authors of L.Y., L.Y., Q.H., Z.K., and L.R. had accomplished the experimental analysis of fluorescence spectra, thermodynamics, FT-IR spectra and UV-Vis spectra as collaborators. Y.X. had accomplished the analysis of molecular docking, while L.Y. and L.J. had mainly taken part in the experimental discussion.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Yongchun Liu
    • 1
  • Yajun Li
    • 2
  • Xiaojun Yao
    • 3
  • Yingying Li
    • 1
  • Huili Qi
    • 1
  • Kejun Zhang
    • 1
  • Ruixia Lei
    • 1
  • Jianning Liu
    • 1
  1. 1.College of Chemistry and Chemical Engineering, Longdong UniversityQingyangP. R. China
  2. 2.No. 203 Research Institute of Nuclear InductryXianyangP. R. China
  3. 3.College of Chemistry and Chemical Engineering, Lanzhou UniversityLanzhouP. R. China

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