“New Gas-phase Tools for the Simultaneous Determination of Protein Complex Structure, Stability and Sequence”
Professor Brandon Ruotolo, University of Michigan, Department of Chemistry
The next generation of medicines will rely heavily upon our ability to quickly assess the structures and stabilities of large, complex macromolecular machines, as well as the influence of large libraries of conformationally-selective small molecule binders and protein-based biotherapeutics. Such endeavours are nearly insurmountable with current tools. In this presentation, I will discuss recent developments surrounding the activation of gas-phase protein complex ions aimed at bridging this gap in basic technology.
“High-Throughput Direct Analysis With IR-MALDESI-MS”
Mans Ekelof, Laboratory of Professor David Muddiman, North Carolina State University, Department of Chemistry
The ability to rapidly and accurately characterize samples is of critical importance in the drug discovery process as well as in the clinical laboratory. However, for many screens and assays, the benefits of mass spectrometry analysis are outweighed by sample compatibility concerns and low throughput. Modern mass analyzers are fast and sensitive enough for most high throughput applications, so the main factors limiting throughput are the processes of sample introduction, separation and ionization.
In the IR-MALDESI approach to high-throughput mass spectrometry, an IR laser is used to aerosolize a solution directly from a suitable target such as the wells of a commercial microtiter plate. Analytes are desorbed and ionized from the ejected droplets through interactions with an intersecting electrospray plume, effectively combining sampling, extraction and ionization into a single concerted step. This electrospray post-ionization mechanism produces ions similarly to ESI-MS, but with higher tolerance for the presence of salts, surfactants and other contaminants. We demonstrate the analytical usefulness and limitations of this method with a selection of published and unpublished experiments, including reaction screening, real time reaction monitoring, and cell differentiation.