A supplement providing a snapshot of the latest developments in chemical biology
Proteins under pressure reveal all
03 October 2006
A new method for determining the performance of proteins used in medicinal tablets could have major benefits for the drug industry.
Proteins make attractive drugs because of their high biological activities, but they can be sensitive to the physical processes used in tablet manufacture. This means that their activities need to be checked during processing, a procedure that normally involves time-consuming 'wet' chemistry techniques. Now, Makoto Otsuka at Musashino University, Tokyo, Japan, and colleagues have developed a protein test that can be performed on the drugs in powder form. This results in savings in terms of cost, time and accuracy, said Otsuka.
Two-dimensional infrared spectra were used to analyse protein tablets
To demonstrate their technique, Otsuka and colleagues took samples of an enzyme called trypsin, and compressed them at different pressures. In each case, they measured the biological activity using conventional 'wet' techniques, and recorded the infrared spectrum. The team were able to develop a formula correlating the appearance of certain peaks in the spectrum with a protein's activity. The team used the formula to evaluate protein performance from infrared data, with 'almost the same accuracy' as the conventional method, said Otsuka.
Otsuka suggests that the underlying reason for the method's success is that changes in protein shape are reflected in the bonding interactions between various parts of the molecule. Variations in these can be picked out simply by looking for changes in the infrared spectrum. The method should enable the pharmaceutical industry to evaluate the stability of a drug in solid-dosage form both quickly and efficiently, said Otsuka.
M Otsuka, Y Fukui, K Otsuka and Y Ozaki, Analyst, 2006, 131, 1116-1121