Chemosynthesis and characterization of site-specific N-terminally PEGylated Alpha-momorcharin as apotential agent
| Autor: | Yao Meng, Gangrui Li, Xu Zhang, Yanfa Meng, Wenkui Sun, Haowen Zhang, Jinghui Sun, Lin-Li Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Ethylene Glycol Momordica charantia lcsh:Medicine Antineoplastic Agents Article 03 medical and health sciences chemistry.chemical_compound Mice Cell Line Tumor PEG ratio medicine Animals Humans lcsh:Science Protein secondary structure Aldehydes Mice Inbred BALB C Multidisciplinary Edman degradation Chemistry Immunogenicity lcsh:R Trypsin In vitro 030104 developmental biology Biochemistry A549 Cells Seeds PEGylation lcsh:Q Ethylene glycol medicine.drug HeLa Cells |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) |
| ISSN: | 2045-2322 |
| Popis: | Alpha-momorcharin (α-MC), a type I ribosome-inactivating protein (RIP) isolated from Momordica charantia seeds, has been extensively studied for its antitumor, antiviral and antifungal activities. However, as an exogenous protein, problems associated with short half-life and strong immunogenicity have limited its clinical application. Poly (ethylene glycol) (PEG), as a polyether compound, is a well established and efficient modifier to develop it as a potential agent. Nevertheless, conventional PEGylation is not site-controlled and the conjugates are often not homogenous due to the generation of multi-PEGylated derivatives. To obtain a homogenous mono-PEGylated α-MC, the PEGylation was carried out by coupling a 20 kDa mPEG-butyraldehyde (mPEG-ALD) with α-MC. The product was separated and purified by MacroCap SP chromatography. Results from SDS-PAGE and MALDI-TOF MS revealed that the PEGylated α-MC consisted of one molecule mPEG and α-MC. Edman degradation confirmed that the N-terminal residue of α-MC was successfully coupled with mPEG-ALD. The mono-PEGylated α-MC possessed an extremely similar secondary structure to native α-MC through spectral analyses. In addition, it also showed low immunogenicity by double immunodiffusion and preserved moderate antitumor activity to three kinds of tumor cell lines in vitro. Finally, trypsin resistance was also considerably improved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|