Back to Journals » International Journal of Nanomedicine » Volume 7

Preparation of an antitumor and antivirus agent: chemical modification of α-MMC and MAP30 from Momordica Charantia L. with covalent conjugation of polyethyelene glycol

Authors Meng Y, Liu S, Li J, Meng Y, Zhao X

Received 7 February 2012

Accepted for publication 14 April 2012

Published 27 June 2012 Volume 2012:7 Pages 3133—3142

DOI https://doi.org/10.2147/IJN.S30631

Review by Single-blind

Peer reviewer comments 2

Video abstract presented by Yao Meng

Views: 132

Yao Meng,1,2 Shuangfeng Liu,1 Juan Li,3 Yanfa Meng,3 Xiaojun Zhao2,4

1
School of Medical Laboratory Science, Chengdu Medical College, Chengdu, China; 2West China Hospital Laboratory of Nanomedicine and Institute for Nanobiomedical Technology and Membrane Biology, Sichuan University, Chengdu, China; 3Key Laboratory of Bio-resources and Eco-environment Ministry of Education/Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, College of Life Science, Sichuan University, Chengdu, China; 4Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

Background: Alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30) derived from Momordica charantia L. have been confirmed to possess antitumor and antivirus activities due to their RNA-N-glycosidase activity. However, strong immunogenicity and short plasma half-life limit their clinical application. To solve this problem, the two proteins were modified with (mPEG)2-Lys-NHS (20 kDa).
Methodology/principal findings: In this article, a novel purification strategy for the two main type I ribosome-inactivating proteins (RIPs), α-MMC and MAP30, was successfully developed for laboratory-scale preparation. Using this dramatic method, 200 mg of α-MMC and about 120 mg of MAP30 was obtained in only one purification process from 200 g of Momordica charantia seeds. The homogeneity and some other properties of the two proteins were assessed by gradient SDS-PAGE, electrospray ionization quadruple mass spectrometry, and N-terminal sequence analysis as well as Western blot. Two polyethylene glycol (PEG)ylated proteins were synthesized and purified. Homogeneous mono-, di-, or tri-PEGylated proteins were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The analysis of antitumor and antivirus activities indicated that the serial PEGylated RIPs preserved moderate activities on JAR choriocarcinoma cells and herpes simplex virus-1. Furthermore, both PEGylated proteins showed about 60%–70% antitumor and antivirus activities, and at the same time decreased 50%–70% immunogenicity when compared with their unmodified counterparts.
Conclusion/significance: α-MMC and MAP30 obtained from this novel purification strategy can meet the requirement of a large amount of samples for research. Their chemical modification can solve the problem of strong immunogenicity and meanwhile preserve moderate activities. All these findings suggest the potential application of PEGylated α-MMC and PEGylated MAP30 as antitumor and antivirus agents. According to these results, PEGylated RIPs can be constructed with nanomaterials to be a targeting drug that can further decrease immunogenicity and side effects. Through nanotechnology we can make them low-release drugs, which can further prolong their half-life period in the human body.

Keywords: ribosome-inactivating proteins, alpha-momorcharin, momordica anti-HIV protein, antitumor, antivirus, (mPEG)2-Lys-NHS (20 kDa), immunogenicity

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other article by this author:

Readers of this article also read:

Spotlight on tavaborole for the treatment of onychomycosis

Jinna S, Finch J

Drug Design, Development and Therapy 2015, 9:6185-6190

Published Date: 20 November 2015

Emerging and future therapies for hemophilia

Carr ME, Tortella BJ

Journal of Blood Medicine 2015, 6:245-255

Published Date: 3 September 2015

A new recombinant factor VIII: from genetics to clinical use

Santagostino E

Drug Design, Development and Therapy 2014, 8:2507-2515

Published Date: 12 December 2014

Purification and in vitro antioxidant activities of tellurium-containing phycobiliproteins from tellurium-enriched Spirulina platensis

Yang F, Wong KH, Yang YF, Li XL, Jiang J, Zheng WJ, Wu HL, Chen TF

Drug Design, Development and Therapy 2014, 8:1789-1800

Published Date: 9 October 2014

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Simple filter microchip for rapid separation of plasma and viruses from whole blood

Wang SQ, Sarenac D, Chen MH, Huang SH, Giguel FF, Kuritzkes DR, Demirci U

International Journal of Nanomedicine 2012, 7:5019-5028

Published Date: 17 September 2012