“…something that a thing has naturally and is part of their basic character” *
The word native can be applied to people or things and can be used as an adjective or a noun. When we talk about the analysis of proteins in their ‘native’ form, we are referring to a state which is as natural and untouched, unperturbed or processed as possible. It almost sounds crazy that you would consider analysing proteins in any other form, but the analysis of proteins is not quite so straightforward.
The fastest growing group of biopharmaceuticals are the monoclonal antibody (mAb)-based therapeutics. Monoclonal antibodies are large (ca. 150 kDa), heterogeneous proteins which are far from inert in nature. They are prone to bind and interact with any molecules or elements that they encounter and to become modified as a direct result of their environment or exposure to other chemicals/molecular entities. Modified mAb variants can exhibit increased or decreased specificity, efficacy and/or immunogenicity than the main drug product, so their presence must be very carefully monitored and controlled throughout the manufacturing process. There are various analytical techniques that can be used to monitor and interrogate the structure and critical quality attributes of proteins; mass spectrometry (MS) is often viewed as the gold standard, based on the level of detail and accuracy that it affords – but not all mass spectrometers natively excel at this.
Proteins have layers of structural complexity, as discussed in one of my earlier blog posts, and maintaining the tertiary, or even quaternary structure of a protein – the native form – from the liquid, into the gas phase and on through the flight path of a complex modern mass spectrometer is no mean feat –in the words of the late Nobel laureate John Fenn in 2002, it’s like giving:
With the latest generation of Orbitrap mass spectrometers, specifically the Thermo Scientific Q Exactive BioPharma Platform, the analysis of intact proteins by MS really couldn’t be simpler. In fact, the analysis of intact proteins is now native to the Orbitrap.
If you want to find out more about the analysis of complex biotherapeutics in their native, denatured and subunit forms make sure you join our 2-part webinar series where experts from Thermo Fisher Scientific and Genentech will share their secrets to success so that you, too, can get full structural insights, simply.
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Check out the latest Orbitrap intact mass analysis posters and presentations
Poster: Integrated characterization of a lysine-linked antibody-drug conjugate by native intact mass analysis and peptide mapping performed on a hybrid quadrupole-Orbitrap mass spectrometer with high mass range
*Source: Cambridge Advanced Learner’s Dictionary & Thesaurus, Cambridge University Press