Protein Engineering and Construct Screening
High throughput protein stability screening of construct libraries is an established technique used to quickly identify the best candidates for downstream processing. Having the most stable form of the protein, for example, an engineered antibody is a solid basis for further optimisation work before forwarding the candidates to the next steps of development. Often involving thousands of early candidates this can be a time-consuming and expensive process. With the SUPR range, of thermal and chemical melt options, stability screening has never been more efficient. High throughput differential scanning fluorimetry using microplate technology, in either 96- or 384-well formats with the inherent ability to prepare the samples in automated systems already being used for other steps of the process means a far higher number of constructs can be screened quickly and without the added workload and cost associated with other techniques. Particularly important at this stage is the low sample usage as there are always limited amounts of samples. Use of thermal melts with the SUPR-DSF yields the best options in a matter of a few hours, not days and further, preferred candidates can be screened orthogonally with the data richness of SUPR-CM chemical melts.
Formulation and Stability Prediction
Once candidates have passed through early development and optimisation stages, it is important to understand how they will be stored, transported, and what safe lifetimes they can have before use. Testing multiple formulations under a range of conditions is essential to the understanding and prediction of long-term stability. Having automatable microplate reader technology combining thermal and chemical melt options can quickly identify the best conditions applied by ranking all formulations in stability thus suggesting which will be most stable in storage. Fast, data-rich information gives insight into both thermodynamic and kinetic stabilities, leading to confidence in decisions about which formulations should be used.
Protein-Ligand Binding Studies
Binding analysis studies are a crucial area of drug development when either screening for hits or working on an optimisation study. The characterisation of the interaction between protein target and ligand, and the KD (Dissociation constant) parameter are critical in selecting the best candidates for further development. With high data quality, false positives or negatives can be eliminated and thus avoid issues of progressing candidates with non-specific binding. Orthogonal approaches are frequently employed to ensure the robustness of decision-making based on the best data available.
Interactions analysis by the SUPR-DSF offers label-free measurements across a wide analyte binding concentration range. The measurements are free in solution and are not influenced by surface effects, mass transport or refractive index buffer issues thus providing the perfect complementary data to more traditional binding analysis techniques. With high throughputs, low sample usage, and easy processing in 384-well plate format, orthogonal data has never been easier.
