Evolution of ComInnex’s Building Blocks for DNA-encoded libraries (DELs)What is common in life on Earth as we know it and the drug discovery industry we are working in? I guess you could say many things, but the answer I am looking for lies in the beautifully complex nature of DNA molecules. Changes in their structure led to the evolution of species over time, and now the very same biological unit is revolutionizing early phase drug discovery all over again, though in a totally different way. Rather than applying structural modifications to the biopolymer strands, this time, scientists are using bits of them as barcodes to label the next generation of drug molecules. First proposed in 1992, the DEL approach was to provide an alternative solution to high-throughput screening (HTS), which tend to be quite laborious and expensive, not to mention the low success rate they were sometimes showing.1 Reaching back to the principles of combinatorial chemistry and teaming up with molecular biology this novel technology quickly showed to overcome many problems making it possible to create, store and screen billions of compounds in just one simple vial.
Why am I bringing this up on our blog? Well, the reason is simple. ComInnex is being quite active in this area from the synthetic chemistry point of view. Namely, we are designing and synthesizing chemical building blocks (BBs) that later on our partners can make to react with each other or connect to DNA bits in line of creating libraries containing a vast amount of labeled drug-likes. And as life and drug discovery are constantly evolving through time we are also developing new and novel compounds to be tested and used.
Our selection started not long ago with bifunctional amino acids, which had the amine group protected (e.g. Fmoc, Boc, esters) and a variety of R-groups hanging from the scaffold. This, in the next round, we have developed further to BBs containing groups of carboxylic acids, amines, alkynes, heteroaryl halides as well as phenolic -OH, and we now have 100s of validated units.