Casting light on proteins: Biacore's gold-coated chip.

How proteins interact with each other has become a key issue in drug discovery and development. Once a target for a drug is identified, it is also important to define how strongly it binds to other biomolecules to obtain information about selectivity. Biacore of Uppsala, Sweden, has been producing affinity-based sensor chips and instrumentation for protein-interaction analysis for more than a decade. The company's core technology is surface plasmon resonance (SPR), using a gold-coated glass chip onto which an array of protein-binding samples is immobilized. When the chip is illuminated, the interaction results in mass changes in the aqueous layer close to the sensor chip, that directly correlate to the refractive-index change. When molecules in the test solution bind to, or dissociate from, the immobilized protein, the refractive index rises and falls and a change is detected. Plotting the response against time allows continuous, real-time monitoring of interacting molecules. Because there is no need to label targets with fluorescent or radioactive labels, molecules can be studied in a near-native state, and the binding data closely reflect in vivo behaviour. Biacore has also developed the technology towards direct measurement of small-molecule binding to protein, for lead optimization in drug discovery, says Stephan Lofas, chief scientific officer. The company markets a variety of SPR instruments to suit different needs, from the high-throughput lab that requires unattended, fully automated runs for up to 384 samples at a time, to the smaller laboratory where researchers want to study a variety of different molecules.

The 8500 Affinity Chip Analyzer from Applied Biosystems, developed in conjunction with HTS Biosystems in Hopkinton, Massachusetts, is based on grating-coupled SPR technology. “If you are interested in target discovery, this system provides massively parallel detection of hundreds of binding events per analysis — thousands per day,” says Enrico Picozza, chief technology officer at HTS Biosystems.

L.M.