Addressing the current needs of drug discovery using Microcalorimetry

Isothermal titration calorimetry (ITC) and Differential Scanning Calorimetry (DSC) are two powerful microcalorimetry techniques that can provide valuable insight into a biomolecule’s behaviour and stability in formulation.

There is widespread recognition within the industry that, when it comes to comprehensively understanding biomolecular interactions, no singular approach holds all the answers. Spectroscopic analysis can use low sample volumes but are often unsuitable for this application, due to inherent weaknesses including dye interference, scattering, poor/no signal, and poorly defined sub domain structural information. In contrast ITC and DSC can provide accurate and highly reproducible thermal measurements which gives researchers further insights into how a potential drug interacts with the target.

Isothermal Titration Calorimetry (ITC) measures the heat released or absorbed during a biomolecular binding event. This allows accurate determination of binding constants (KD), reaction stoichiometry (n), enthalpy (∆H), and entropy (ΔS). Differential Scanning Calorimetry (DSC) measures heat changes that occur in the biomolecule during a controlled increase or decrease in temperature. Understanding the factors which affect both binding behaviour and stability are critical in the design, formulation and the optimisation of drug manufacturing processes.

Recent advances in thermodynamic analysis however have raised many new challenges. One of the most recognised challenges is the need to evaluate a wide range of binding affinities (KD) which can span from low millimolar to the subnanomolar range. Another is to precisely categorise and differentiate low molecular weight ligands based on the mechanism of action, affinity and energetics of interaction. Factors that can complicate the reliable interpretation of binding data include incorrect assessment of protein concentration and the presence of an inactive protein fraction. In addition, interpretation of this data can also be complicated by uncertainty regarding the concentration of compound stocks, which can arise as a result of limited solubility, incorrect measurement or chemical dissimilarities between compounds.

The new Malvern MicroCal PEAQ ITC and DSC systems have many integrated features that address all these challenges and more making them the ideal tool to generate reproducible and reliable data with ease.

MicroCal PEAQ-ITC: Gold Standard for measuring binding affinities of more interactions than any other technique.

The new MicroCal PEAQ-ITC is the ideal instrument for measuring binding affinity and stoichiometry.

New software makes it easy for anyone to use this system. It has built in videos showing how to run an experiment, design tools showing how much sample to use to optimise the experiment and data quality checks. The fast response time of the instrument has a significant effect on sensitivity allowing for lower sample consumption and reducing the experimental time. A KD can be determined in less than 30 minutes including all the analysis. The instrument can also be fully automated for complete “hands-free” operation. The analysis allows for the determination of the active concentration of the target protein or the ligand concentration or both when the appropriate controls are used. New software tools simplify the fitting of complex binding isotherms that may be observed when titrating with enantiomeric mixtures, competition experiments or with targets with more than one binding site.

MicroCal PEAQ-DSC: Gold Standard artifact-free, and reproducible stability data for all proteins in all buffers.

The new MicroCal PEAQ-DSC Automated system delivers high throughput, highly sensitive protein stability analysis with low sample consumption, in an automated platform. Unattended operation enables 24-hour screening, while the integrated software facilitates non-subjective data analysis, performance qualification and compliance with 21 CFR Part 11 and Annex 11 regulations, all delivering high integrity data and driving productivity in biopharmaceutical research.

For more information on the new Malvern MicroCal PEAQ ITC and DSC please contact us.

ATA Scientific Pty Ltd
+61 2 9541 3500
enquiries@atascientific.com.au
www.atascientific.com.au