Automated measurement of protein conformation
A stable, native conformation isessential to the correct functioning of a protein. Failure to foldinto the correct conformation will cause the protein to exhibitdifferent properties, making it at best inactive or, worse, toxicor immunogenic. Circular dichroism (CD) spectroscopy is a sensitiveprobe of protein conformation but is not used more routinelybecause of the perception that it is a labour intensive,low-productivity technique whose results require expertinterpretation. In this talk, we shall show how CD can be usedearly in the development cycle to give additional insights into thelikelihood of future success for bio-therapeutic candidates. Wewill describe a system that:
- sequentially delivers samples tothe spectrometer cuvette from a microtitre plate with effectivelyzero inter-sample carry-over
- automatically acquires and storesspectroscopic data for up to 384 (4 x 96-well plate) sampleswithout operator intervention
- recovers sample to minimizewaste
- simultaneously measures more thanone optical property (e.g. CD and absorption) to maximize theinformation return per sample
- interfaces seamlessly with datareduction programs designed to simplify the interpretation ofspectroscopic data
Examples using model proteinsand those typical in bio-therapeutic development will bepresented.