Autor: |
Puchkov IA, Kononova NV, Bobruskin AI, Bairamashvili DI, Mart'ianov VA, Shuster AM |
Jazyk: |
ruština |
Zdroj: |
Bioorganicheskaia khimiia [Bioorg Khim] 2012 Sep-Oct; Vol. 38 (5), pp. 545-54. |
DOI: |
10.1134/s1068162012050111 |
Abstrakt: |
In order to create an active pharmaceutical substance of the drug with prolonged action the modification of recombinant human granulocyte colony-stimulating factor GCSF (filgrastim) with polyethylene glycol (PEG, M 21.5 kDa) was conducted. A method for preparation of PEG-filgrastim designed for the development and scaling-up of the technological process of production was described. Modification of proteins with PEG was performed by selective covalent attachment of the molecule alpha-methyl-PEG-propionaldehyde to the alpha-amino group of the N-terminal methionine amino acid residue of the recombinant GCSF. The conditions of the reaction, which provide the desired product yield at least 85% of the total protein, also high protein concentration in the reaction mixture (more than 9 mg/mL) and reduce consumption of PEG in terms of terminal alpha-amino group of the protein was chosen. The data of RP HPLC and MALDI-mass spectrometry showed that the produced drug modified by the N-terminal residue and contains no more than 10% of products with a high degree of modification. |
Databáze: |
MEDLINE |
Externí odkaz: |
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