Several years ago a new method of screening for drug candidates was identified which took advantage of principles which are based around evolutionary biology. This method, called dynamic combinatorial chemistry (DCC) uses a library of molecules which can combine, separate and recombine in new ways. In this way the library contains what is effectively a huge amount of molecular Lego which can be put together to form a huge variety of different things just as the same Lego bricks can make a house, a tree or even a dragon. If a target, such as an enzyme which you want to block, is added to the mixture then any of these randomly combined molecules which bind to the enzyme are stabilised. As such, these molecules become enriched within the population at the expense of other molecules.
In this way drug design is approximating to an evolutionary process although there isn’t the reproduction of successful molecules, instead there is the selective accumulation of these ‘fitter’ molecules. This method is far from perfect however since in order for the process to work covalent bonds need to be formed, broken and reformed. That isn’t too much of a problem when using DCC to bind inorganic molecules, but the conditions for using it with biological molecules are much more stringent since the biological target is much more eaily damaged, which damage would prevent it being used as a template. As such, only a reduced number of reactions can currently be catalysed and this leads to a restricted number of molecules being formed. This will hopefully be remedied in the future and could lead to a much more rapid process of not only drug discovery but also more efficient optimisation. This could occur qiuckly since once a lead has been found a more restricted library can be created allowing for finer optimisation to take place using the original molecule as an initial template.
This stage of research is clearly not the only part of the drug discovery process. It is also not the most expensive part, compared with animal tests and subsequent clinical trials. However, if every step can be improved just a bit maybe we can hope to see a solution to the problem with drug discovery and the developing world.
Written by Ed Roberts