Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-Ethylcamptothecin

A previous study showed that intravenous immunoglobulin (IVIG) could preserve higher levels of biologically active lactone moieties of topotecan, 7-ethyl-10-hydroxycamptothecin (SN-38) and 10-hydroxycamptothecin at physiological pH 7.40. As one of camptothecin analogues (CPTs), the interaction of 7-...

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Main Authors: Yong-Chun Liu, Ying-Ying Li, Xiao-Jun Yao, Hui-Li Qi, Xiao-Xia Wei, Jian-Ning Liu
Format: Article
Language:English
Published: MDPI AG 2018-09-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/23/9/2389
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author Yong-Chun Liu
Ying-Ying Li
Xiao-Jun Yao
Hui-Li Qi
Xiao-Xia Wei
Jian-Ning Liu
author_facet Yong-Chun Liu
Ying-Ying Li
Xiao-Jun Yao
Hui-Li Qi
Xiao-Xia Wei
Jian-Ning Liu
author_sort Yong-Chun Liu
collection DOAJ
description A previous study showed that intravenous immunoglobulin (IVIG) could preserve higher levels of biologically active lactone moieties of topotecan, 7-ethyl-10-hydroxycamptothecin (SN-38) and 10-hydroxycamptothecin at physiological pH 7.40. As one of camptothecin analogues (CPTs), the interaction of 7-ethylcamptothecin and IVIG was studied in vitro in this study. It was shown that the main binding mode of IVIG to 7-ethylcamptothecin was hydrophobic interaction and hydrogen bonding, which is a non-specific and spontaneous interaction. The hydrophobic antigen-binding cavity of IgG would enwrap the drug into a host-guest inclusion complex and prevent hydrolysis of the encapsulated drug, while the drug is adjacent to the chromophores of IgG and may exchange energy with chromophores and quench the fluorescence of the protein. Also, the typical β-sheet structure of IVIG unfolded partially after binding to 7-ethylcamptothecin. Additionally, the binding properties of IVIG and six CPTs with different substituents at A-ring and/or B-ring including camptothecin, topotecan, irinotecan, 10-hydroxycamptothecin, 7-ethylcamptothecin and SN-38 were collected together and compared each other. Synergizing with anti-cancer drugs, IVIG could be used as a transporter protein for 7-ethylcamptothecin and other CPTs, allowing clinicians to devise new treatment protocols for patients.
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spelling doaj.art-5462d07dea15486690b6b5c03be19d312022-12-21T19:43:29ZengMDPI AGMolecules1420-30492018-09-01239238910.3390/molecules23092389molecules23092389Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-EthylcamptothecinYong-Chun Liu0Ying-Ying Li1Xiao-Jun Yao2Hui-Li Qi3Xiao-Xia Wei4Jian-Ning Liu5College of Chemistry and Chemical Engineering, Longdong University, Qingyang 745000, ChinaCollege of Chemistry and Chemical Engineering, Longdong University, Qingyang 745000, ChinaCollege of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, ChinaCollege of Chemistry and Chemical Engineering, Longdong University, Qingyang 745000, ChinaCollege of Chemistry and Chemical Engineering, Longdong University, Qingyang 745000, ChinaCollege of Chemistry and Chemical Engineering, Longdong University, Qingyang 745000, ChinaA previous study showed that intravenous immunoglobulin (IVIG) could preserve higher levels of biologically active lactone moieties of topotecan, 7-ethyl-10-hydroxycamptothecin (SN-38) and 10-hydroxycamptothecin at physiological pH 7.40. As one of camptothecin analogues (CPTs), the interaction of 7-ethylcamptothecin and IVIG was studied in vitro in this study. It was shown that the main binding mode of IVIG to 7-ethylcamptothecin was hydrophobic interaction and hydrogen bonding, which is a non-specific and spontaneous interaction. The hydrophobic antigen-binding cavity of IgG would enwrap the drug into a host-guest inclusion complex and prevent hydrolysis of the encapsulated drug, while the drug is adjacent to the chromophores of IgG and may exchange energy with chromophores and quench the fluorescence of the protein. Also, the typical β-sheet structure of IVIG unfolded partially after binding to 7-ethylcamptothecin. Additionally, the binding properties of IVIG and six CPTs with different substituents at A-ring and/or B-ring including camptothecin, topotecan, irinotecan, 10-hydroxycamptothecin, 7-ethylcamptothecin and SN-38 were collected together and compared each other. Synergizing with anti-cancer drugs, IVIG could be used as a transporter protein for 7-ethylcamptothecin and other CPTs, allowing clinicians to devise new treatment protocols for patients.http://www.mdpi.com/1420-3049/23/9/2389intravenous immunoglobulin (IVIG)camptothecin analogues (CPTs)7-ethyl-camptothecindrug deliveryprotein-drug interaction
spellingShingle Yong-Chun Liu
Ying-Ying Li
Xiao-Jun Yao
Hui-Li Qi
Xiao-Xia Wei
Jian-Ning Liu
Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-Ethylcamptothecin
Molecules
intravenous immunoglobulin (IVIG)
camptothecin analogues (CPTs)
7-ethyl-camptothecin
drug delivery
protein-drug interaction
title Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-Ethylcamptothecin
title_full Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-Ethylcamptothecin
title_fullStr Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-Ethylcamptothecin
title_full_unstemmed Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-Ethylcamptothecin
title_short Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-Ethylcamptothecin
title_sort binding performance of human intravenous immunoglobulin and 20 s 7 ethylcamptothecin
topic intravenous immunoglobulin (IVIG)
camptothecin analogues (CPTs)
7-ethyl-camptothecin
drug delivery
protein-drug interaction
url http://www.mdpi.com/1420-3049/23/9/2389
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