Publication date: Available online 16 February 2017 Source:Journal of Pharmaceutical and Biomedical Analysis
Author(s): Derek J. Hodgson, Yves Aubin
A number of recombinant protein therapeutic products, such as filgrastim (methionyl granulocyte colony stimulating factor [Met-GCSF] used to boost the immune system in chemotherapy treated cancer patients), and interferon alpha-2 (used for the treatment of various viral infections), have been chemically modified with the addition of a polyethylene glycol (PEG) chain. This modification prolongs residency of the drug in the body and reduces metabolic degradation, which allows less frequent administration of the products. Here we show how NMR spectroscopy methods can assess the higher order structure (HOS) of pegylated-filgrastim ( ), pegylated interferon-?2a ( ) pegylated interferon-?2b ( ) purchased from the marketplace. The addition of the PEG moiety effectively doubles the molecular weight of the three products. This presents a significant challenge for the application of NMR techniques. Nevertheless, the results showed that high-resolution spectra could be recorded for two of the three products. Comparison of the spectra of the pegylated protein and the non-pegylated protein shows that the chemical modification did not alter the HOS of these proteins.
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PEGylation is an attractive approach to modifying oligonucleotides intended for therapeutic purposes. PEG conjugation reduces protein interactions with the oligonucleotide, and helps to overcome their intrinsic biopharmaceutical shortcomings, such as poor enzymatic stability, rapid body clearance, and unwanted immunostimulation. However, the effect of PEG architecture and the manner in which the PEG component interferes with the hybridization of the oligonucleotide...
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Study of PEGylated model protein reveals porous structure based on PEG size - Phys.Org
Study of PEGylated model protein reveals porous structure based on PEG size - Phys.Org
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Study of PEGylated model protein reveals porous structure based on PEG size
Phys.Org
NMR studies using 1H-15N heteronuclear single-quantum correlation spectroscopy showed that the PEG-Pc had well-dispersed resonances that indicated the protein remained folded in a stable conformation. Chemical shift perturbations were only...
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Assessment of the structure of pegylated-recombinant protein therapeutics by the NMR fingerprint assay
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