National Physical Laboratory

Protein conformational changes and aggregation: analysis, troubleshooting and quantification

Protein conformational changes and aggregation: analysis, troubleshooting and quantification 

Protein aggregation has been recognised as a bottleneck in the diagnostic sector and represents a major problem in the drug delivery pipeline in the biopharmaceutical industry. Aggregation can affect different stages along the drug development process. In the early development it can affect product activity and function therefore leading to erroneous drug evaluation results. More importantly it affects the pre-formulation and formulation phases where suitable solutions conditions are scouted to provide the further stages of pre-clinical and clinical development with a stable, active and safe drug. Another area heavily affected is Down Stream Processing where aggregation can cause delays in production, which are costly to resolve.The array of biophysical techniques available in the Biotechnology laboratories at NPL can be used to provide complementary information about protein structure, function, assembly and activity (binding or in vitro assays). This provides the knowledge base that, when coupled with our expertise in the field of protein structure-function, can help to find valuable solutions to those issues that very often represent bottlenecks along the product development pipeline.

With particular focus on protein aggregation we can provide the following information:

  • Secondary structure: CD (far-UV) and FTIR

  • Tertiary structure: CD (near-UV), Intrinsic Fluorescence, fluorescence-quenching studies with different quenchers, dye binding (i.e. ANS)

  • Thermodynamic stability: Temperature Denaturation Measurements (CD, FTIR and DLS)

  • Colloidal stability: SLS and Zeta Potential measurements

  • Aggregation state: DLS, SEC –HPLC, SDS-PAGE, PAGE

  • Activity: Classical enzyme kinetics

  • Binding: ITC, Biacore, ELISA

Contact

Customer Service tel: +44 20 8943 8637
E-mail: bioanalytical_enquiries@npl.co.uk

Last Updated: 18 Aug 2015
Created: 5 May 2009

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