Assessment of the structure of pegylated-recombinant protein therapeutics by the NMR fingerprint assay.
Related Articles Assessment of the structure of pegylated-recombinant protein therapeutics by the NMR fingerprint assay.
J Pharm Biomed Anal. 2017 Feb 16;138:351-356
Authors: Hodgson DJ, Aubin Y
Abstract
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 (Neulasta®), pegylated interferon-?2a (Pegasys®) pegylated interferon-?2b (PEG-Intron®) 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.
PMID: 28254519 [PubMed - as supplied by publisher]
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