Shedding light on protein aggregation with the Litesizer 500

Therapeutic proteins, such as antibodies, hormones, enzymes, growth factors, etc., are highly successful in the clinic and are currently a major focus of the pharmaceutical industry. However, formulation of stable protein drugs is challenging, as most proteins are sensitive to sunlight, high and low temperatures, pH, and so on. Exposure to these conditions can lead to irreversible denaturation or to aggregation.

Protein aggregates lead to a loss of biological activity of the drug and can cause severe adverse reactions in the patients. Protein aggregation can be monitored rather simply by using light scattering techniques. Particle size and particle mass can be measured quickly and conveniently by using dynamic and static light scattering, respectively. Furthermore, the transmittance can also provide a very rapid indication of the extent of aggregation. All three of these techniques are available in the one instrument with the Litesizer™ 500.

An excellent case study for examining the aggregation behavior of pharmaceutical proteins is human insulin, a peptide hormone that is used to treat diabetes mellitus. Insulin is secreted as a monomer but can co-assemble into dimers at low pH. At neutral pH and in the presence of zinc ions these dimers further aggregate into hexamers, which constitute the most stable form of the protein. But because insulin’s receptor only binds the monomeric form, insulin oligomers are biologically inactive and must undergo dissociation to exert their effect. This has been largely exploited by the pharmaceutical industry, with zinc-stabilized hexameric insulin being used in long-acting formulations while dimeric insulin or monomeric insulin analogs act as short- or rapid-acting variants. 

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