Related ArticlesAssessment 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]
Assessment of the structure of pegylated-recombinant protein therapeutics by the NMR fingerprint assay
Assessment of the structure of pegylated-recombinant protein therapeutics by the NMR fingerprint assay
Publication date: Available online 16 February 2017
Source:Journal of Pharmaceutical and Biomedical Analysis</br>
Author(s): Derek J. Hodgson, Yves Aubin</br>
A number of recombinant protein therapeutic products, such as filgrastim (methionyl granulocyte colony stimulating factor 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...
nmrlearner
Journal club
0
02-17-2017 07:32 AM
[NMR paper] Effect of PEG Architecture on the Hybridization Thermodynamics and Protein Accessibility of PEGylated Oligonucleotides
Effect of PEG Architecture on the Hybridization Thermodynamics and Protein Accessibility of PEGylated Oligonucleotides
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...
nmrlearner
Journal club
0
12-29-2016 09:23 PM
[NMR paper] Simple NMR methods for evaluating higher order structures of monoclonal antibody therapeutics with quinary structure.
Simple NMR methods for evaluating higher order structures of monoclonal antibody therapeutics with quinary structure.
Related Articles Simple NMR methods for evaluating higher order structures of monoclonal antibody therapeutics with quinary structure.
J Pharm Biomed Anal. 2016 Jun 7;128:398-407
Authors: Chen K, Long DS, Lute SC, Levy MJ, Brorson KA, Keire DA
Abstract
Monoclonal antibody (mAb) drugs constitute the largest class of protein therapeutics currently on the market. Correctly folded protein higher order structure...
nmrlearner
Journal club
0
06-28-2016 06:25 PM
[NMR paper] Application of Natural Isotopic Abundance (1)H-(13)C- and (1)H-(15)N-Correlated Two-Dimensional NMR for Evaluation of the Structure of Protein Therapeutics.
Application of Natural Isotopic Abundance (1)H-(13)C- and (1)H-(15)N-Correlated Two-Dimensional NMR for Evaluation of the Structure of Protein Therapeutics.
Related Articles Application of Natural Isotopic Abundance (1)H-(13)C- and (1)H-(15)N-Correlated Two-Dimensional NMR for Evaluation of the Structure of Protein Therapeutics.
Methods Enzymol. 2016;566:3-34
Authors: Arbogast LW, Brinson RG, Marino JP
Abstract
Methods for characterizing the higher-order structure of protein therapeutics are in great demand for establishing...
nmrlearner
Journal club
0
01-23-2016 03:35 PM
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
http://www.bionmr.com//t2.gstatic.com/images?q=tbn:ANd9GcQdT1VtDs_349GghNDjMV50tdw7g0UzZNnkRkMt-SgVH2a6hHSvjT8JY4N42n5PGHBQ_JntWNc
Phys.Org
<img alt="" height="1" width="1">
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...
[NMR paper] On the Analytical Superiority of 1D NMR for Fingerprinting the Higher Order Structure of Protein Therapeutics Compared to Multidimensional NMR Methods.
On the Analytical Superiority of 1D NMR for Fingerprinting the Higher Order Structure of Protein Therapeutics Compared to Multidimensional NMR Methods.
Related Articles On the Analytical Superiority of 1D NMR for Fingerprinting the Higher Order Structure of Protein Therapeutics Compared to Multidimensional NMR Methods.
Anal Chem. 2015 Apr 30;
Authors: Poppe L, Jordan JB, Rogers G, Schnier PD
Abstract
An important aspect in the analytical characterization of protein therapeutics is the comprehensive characterization of higher...
nmrlearner
Journal club
0
05-02-2015 09:41 PM
[NMR paper] The X-ray structure of a recombinant major urinary protein at 1.75 A resolution. A co
The X-ray structure of a recombinant major urinary protein at 1.75 A resolution. A comparative study of X-ray and NMR-derived structures.
Related Articles The X-ray structure of a recombinant major urinary protein at 1.75 A resolution. A comparative study of X-ray and NMR-derived structures.
Acta Crystallogr D Biol Crystallogr. 2001 Dec;57(Pt 12):1863-9
Authors: Kuser PR, Franzoni L, Ferrari E, Spisni A, Polikarpov I
Major urinary proteins belong to the lipocalin family and are present in the urine of rodents as an ensemble of isoforms with...
Assessment of the structure of pegylated-recombinant protein therapeutics by the NMR fingerprint assay.
Linear Mode
