Future Directions

Advances in mass spectrometry, especially innovations leading to more efficient ionization techniques and higher sensitivity detector systems, will enable the characterization of protein-ligand binding interactions using ever smaller quantities of purified protein target. Improvements in separation technologies may even allow these techniques to be explored using partially purified protein preparations, or in an especially optimistic view, using unpurified cellular or tissue extracts.

New MS hardware and software designs allow more researchers to utilize MS-based techniques without specialized training. Engineering advances that yield complete ''lab-on-a-chip'' systems are enabling miniaturized chromatography systems that integrate all stages of sample preparation, separation, and introduction to high-sensitivity detector systems. These innovations may lead to the commercial availability of easily accessible instrumentation, so that the techniques presented here will become widely available to researchers in all areas of drug discovery and less limited to specialized laboratories.

Future improvements of the methods presented here will include modifications that enable determination of the thermodynamic parameters of protein-ligand binding interactions. For example, ALIS-based Kd or off-rate measurements at varying temperatures could yield useful relationships between chemical structures and binding thermodynamics. Ready access to such information, especially for targets that otherwise require complex bioassays for their study, could posi tively impact the medicinal chemistry optimization component of the drug discovery process in unanticipated ways.

Was this article helpful?

0 0

Post a comment