Insights into the structure and conformation of biomolecules to understand their biological function for new drug systems using SAXS in the Laboratory

Angelika Scheiflinger-Latal, Franz Pirolt, Heike Ehmann, Andreas Keilbach and Martin Medebacha

aAnton Paar GmbH, Anton Paar Straße 20, 8054 Graz, Austria
angelika.scheiflinger-latal@anton-paar.com

The development of new and better drugs, to overcome diseases like Alzheimer’s disease, Parkinson or antibiotic resistance, are a main focus of research in the biological, pharmaceutical and medical field. In the last decades the interest in biological macromolecules and complexes providing properties to treat and cure diseases has tremendously increased. To understand their biological function in vitro especially small-angle X-ray scattering (SAXS) gains increasing attention offering complementary information to the traditionally used biological techniques. SAXS enables to study the structure and dynamics of biomolecules in solution where physiological key parameters can be tuned and tested.

SAXS is a versatile technique used for shape and size characterization of nanostructured materials between 1 nm and 200 nm. Biological samples, like proteins, peptides, monoclonal antibodies or viruses are already well known to be investigated with SAXS. Furthermore drug delivery systems like drug loaded vesicles, where size and shape parameters of the vesicle and the drug are found or granulate powders, where the internal surface obtained by SAXS correlates with the tablet hardness, are interesting examples of applications.

In the present contribution we show selected applications of biological macromolecules, using a multifunctional laboratory Small and Wide Angle X-ray Scattering (SWAXS) system, the SAXSpoint 2.0. The SAXSpoint 2.0 system is a compact lab-scale system with dedicated point collimation, which enables SAXS, WAXS and grazing-incident (GISAXS) scattering studies under ambient and non-ambient conditions, in-situ tensile SWAXS experiments, and RheoSAXS studies. It satisfies the advanced user with a wide range of dedicated sample stages, full experimental flexibility to meet the right environment for each sample, and highest resolution. The system provides simple operation, short measurement times and excellent angular resolution, enabled by a smart beam formation concept while maintaining a laboratory-friendly compact size and small footprint.

Different SAXS and WAXS studies on biological macromolecules and pharmaceutically relevant samples were performed on the presented SAXSpoint 2.0 system. Some of the samples required high resolution (very low minimum scattering angle) in order to resolve large structural dimensions. The unique sample-positioning mechanism enabled WAXS measurements to determine crystallinity without re-aligning any part of the SWAXS system. The presented studies clearly show that high-resolution and high-quality SWAXS data can be obtained for biological macromolecules and complexes investigated in their native state with a laboratory SWAXS system.