Rapid, femtolitre-scale assays targeted to specific disease proteins will speed up drug discovery, says Hisashi Koga of the Chiba Industry Advancement Center in Japan.

Reverse chemical genetics is a method for drug discovery that tests the interactions between the proteins involved in disease and libraries of compounds. This is a promising method, but few assays for drug screening have been produced so far, said Koga. Koga has developed a strategy to produce biological assays to test small molecule libraries starting with DNA sequences. 

Koga takes DNA sequences associated with disease and uses them to produce the proteins they encode. The proteins are then analysed to discover which other proteins they interact with, giving an idea of which proteins are associated with the disease pathway. From this information a model of the protein biological pathways is made.

The proteins assigned to the disease pathway are tested to find out which segments are involved in the interactions with other proteins. These protein segments are used to screen the compound libraries for potential drugs. With some improvements, this work should lead to 'hundreds of drug screening assays,' said Koga.

Wendy Crocker