Discovery and development of Pd-catalyzed cross-coupling reactions greatly spurred the rise of medicinal chemistry. They also strongly biased the chemical space of potential drugs to biaryl-like compounds. Currently, directed by growing demand for chemical diversity, the field is evolving in the direction of more flexible chemotypes, where rigid scaffolds are connected via single Csp3-Csp3 bonds.
Today chemical biology generates new high-throughput methods of studying biomolecules almost as quickly as organic chemists report total syntheses. Whole genome, transcriptome, proteome, lipidome, glycome etc. analyses are flourishing and delivering vast amounts of data. Bioinformaticist are trying to cope with the data flow by archiving them in various databases. This has led to a situation when the number and diversity of databases became incomprehensible for a human being. Continue reading “The database of databases”
Epigenetics is an exciting but a weird area. It’s well recognized that messing with chromatin and chemical modifications of nucleic acids has profound consequences at the cellular and organism levels. But for me the mechanistic rationale for targeting epigenome pharmacologically was always somewhere close to throwing a monkey wrench into the clockworks and watching what will happen. It seems (not surprisingly) that in fact the effects are more predictable. Continue reading “Epigenetic ant reprogramming”
Since I’ve shifted from ‘pure’ synthetic chemistry lab to chemical biology, my set of labware has also changed from borosilicate glassware to polypropylene plasticware. And, you know what, I wish it happened years earlier. Here are some awesome little things that make my synthetic life easier today. Continue reading “Some things organic chemists should borrow from bio lab”
Fragment-based design is one of my favorite approaches in drug discovery. It has everything from very simple conception to sophisticated data analysis. The most importantly, it works as it’s supposed to. So it’s always entertaining to find a paper from the very founders of FBDD, I mean Astex Pharmaceuticals and Harren Jhoti himself. Continue reading “Finding new pockets with fragments”