dc.contributor.author | Zhao, Xiaojun | |
dc.contributor.author | Meng, Yao | |
dc.contributor.author | Liu, Shuangfeng | |
dc.contributor.author | Li, Juan | |
dc.contributor.author | Meng, Yanfa | |
dc.date.accessioned | 2014-07-01T12:27:10Z | |
dc.date.available | 2014-07-01T12:27:10Z | |
dc.date.issued | 2012-06 | |
dc.identifier.issn | 1178-2013 | |
dc.identifier.issn | 1176-9114 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/88153 | |
dc.description.abstract | 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)[subscript 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. | en_US |
dc.language.iso | en_US | |
dc.publisher | Dove Medical Press | en_US |
dc.relation.isversionof | http://dx.doi.org//10.2147/IJN.S30631 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/ | en_US |
dc.source | Dove Medical Press | en_US |
dc.title | Preparation of an antitumor and antivirus agent: chemical modification of α-MMC and MAP30 from Momordica Charantia L. with covalent conjugation of polyethyelene glycol | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Meng, Yao, Shuanfeng Liu, Juan Li, Yanfa Meng, and Xiaojun Zhao. “Preparation of an Antitumor and Antivirus Agent: Chemical Modification of α-MMC and MAP30 from Momordica Charantia L. with Covalent Conjugation of Polyethyelene Glycol.” International Journal of Nanomedicine (June 2012): 3133. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Center for Biomedical Engineering | en_US |
dc.contributor.mitauthor | Zhao, Xiaojun | en_US |
dc.relation.journal | International Journal of Nanomedicine | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Meng, Yao; Liu, Shuanfeng; Li, Juan; Meng, Yanfa; Zhao, Xiaojun | en_US |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |