Proteins are complex macromolecules that have tertiary and quaternary structural features that may be essential to their biological function and stability. Properly folded proteins are often complexed with ligands and/or other proteins in the cell or within biological membranes. Protein complexes also exist in biological fluids such as serum and cerebral spinal fluid where they may be involved in a variety of physiological or disease-related processes. To gain insight into their structure/function relationships, Larial uses a variety of bioanalytical techniques to monitor changes in protein conformation and interaction kinetics. Often, a single technology is insufficient at addressing all the possible criteria (composition, yield, purity, functionality etc) that a research or quality control scientist must determine prior to moving forward. A variety of bioanalysis techniques such as mass spectrometry, gel electrophoresis and SPR biosensing can be used to evaluate crude or refined protein samples destined for further processing. Scientific algorithms, designed to provide information on complex biological systems or product formulations, require sufficient analytical support at various stages so informed decisions can be made by scientists and managers of R&D programs.

For example, changes in membrane protein conformation can be monitored by partial proteolytic digestion followed by purification and peptide mapping of cleavage sites using mass spectrometry. Similarly, hydrodynamic measurements of a protein's size by gel filtration HPLC or analytical ultracentrifugation provides information regarding changes in a size, shape or interaction with ligands and other proteins. SPR biosensing can be used to measure kinetic interaction rates between proteins or with ligands to evaluate changes in affinities or test the effects of mutations on binding site conformations. The isolation of protein complexes from cells/tissues by co-immunoprecipitation followed by tryptic digestion and mass spectrometry provides a useful technique for identifying and characterizing stable interactions. Generating chemically-tagged protein constructs for in vitro studies (eg., FRET, TRF etc) on protein-protein interactions or measurements of catalytically-induced changes in protein conformation is another support service Larial provides to its clients. Our current portfolio of in-house laboratory assays were designed to provide specifications (eg., antibody-antigen affinity, functional activity, purity) on some of the custom biologicals Larial produces for clients in the academic, biotech, pharma and fermentation sectors.