Development and use of DJ-1 affinity microcolumns to screen and study small drug candidates for Parkinson's disease.

Background: DJ-1 is a protein whose mutation causes rare heritable forms of Parkinson's disease (PD) and is of interest as a target for treating PD and other disorders. This work used high performance affinity microcolumns to screen and examine the binding of small molecules to DJ-1, as could be used to develop new therapeutics or to study the role of DJ-1 in PD. Non-covalent entrapment was used to place microgram quantities of DJ-1 in an unmodified form within microcolumns, which were then used in multiple studies to analyze binding by model compounds and possible drug candidates to DJ-1.

Brain endothelial permeability, transport, and flow assessed over 10 orders of magnitude using the in situ brain perfusion technique.

Background: Cerebral blood flow normally places a limit on the magnitude of brain vascular permeability (P) that can be measured in vivo. At normal cerebral blood flow, this limit falls at the lower end of lipophilicity for most FDA-approved CNS drugs. In this study, we report on two methods that can be used to overcome this limitation and measure brain vascular permeability values that are up to ~1000 times higher using the in situ brain perfusion technique.

Analysis of solution-phase biomolecular interactions by liquid chromatography: General strategies and recent developments.

The analysis of biomolecular interactions is important in characterizing and understanding many fundamental processes that occur in the body and biological systems. A variety of methods are available for studying the extent and rate of binding of these interactions. Some of these techniques are homogeneous methods, with all interacting components being present in the solution-phase, while others are heterogeneous, such as involving both solution-phase and solid-phase components.