Technique evaluates protein-drug interactions

The method, developed by researchers from the UCL Department of Biochemical Engineering and the London Centre for Nanotechnology in collaboration with Cambridge and Sussex universities, is applicable to any free solution protein-drug interaction.

The technique applies microfluidics, using only nanolitres of sample - coupling protein stability and drug affinity analysis to microfluidic devices for sample preparation.

In a paper recently published in the industry journal 'Protein Science' the researchers established a new nanolitre-scale technique in micro-capillaries to measure intrinsic protein fluorescence and obtain accurate protein denaturation curves at equilibrium.

Free energies of protein unfolding were determined by the method and used to determine the affinity of a drug - the immunosuppressant rapamycin - to a protein, the cellular immunophilin FKBP12.

In addition, the microcapillary technique was used to measure the interaction energy between rapamycin and the Phe99 residue of FKBP-12 from a double mutant cycle analysis.

The method utilised combinations of two different protein mutations to study the molecular interactions within a given protein.

Until now, the modus operandi for protein analysis often meant either too much of the biological or compound materials were consumed in large sample volumes, or that chemical labelling with fluorescent tags was required to achieve measurements at sub-microlitre volumes.