Hi guys! Welcome back to day 2 of my RACI congress summary. Once again here is a simple outline of my top 3 talks of the day:
1. David Leigh, The University of Manchester – “Making the tiniest machines”
Out walks David Leigh with coloured cloth in hand, he paces back and forth across the stage. After a short introduction, he opens his hand and the cloth is gone. For those that don’t know, David Leigh is clearly quite the magician – both on stage and in the lab. Leigh described one of the first examples of a “molecular machine” to produce a peptide/protein molecule. Using a supramolecular catenane strategy, a series of amino acids were coupled together using chemical ligation. It will be very interesting to see how this can be applied to large proteins/peptides as opposed to more simplistic models.
2. James Crawford, Genentech – “Potent and selective pyridone BTK inhibitors with activity against mutant forms of BTK”
Building on the work of Roche, Crawford outlined the latest by Genentech for their work toward a BTK inhibitor. Some small molecule structures were described for the first time. A BTK inhibitor was developed using X-Ray crystallographic methods in combination with computational models and what Crawford describes as “Matched Pair Analysis”. This modern technique involves looking at a single property in a series of molecules in which a single functional group is changed/modified. Monitoring the trend of these properties across the series can then drive the med-chem direction of the project. Strikingly, kinase activity/selectivity was constantly monitored throughout the project.
3. Shane Wilkinson, Sydney University – “Synthetic Cannabinoids : from “drug design” to “designer drugs””
The huge explosion of designer drugs has lead to the rapid implementation of “hit to market” drugs – in direct contrast with the “hit to lead” theme in which Wilkinson found himself. An awesome talk on a vast series of street drugs currently being dispersed into the public domain via questionable characters in the illicit drug scene. Shane has synthesised a huge number of these compounds and tested their affinity for the “promiscuous” cannabinoid receptor. The most striking message of the talk was the ability of illicit manufacturers to use academic and patent literature as inspiration for their own organic syntheses. Shane even outlined a few cases where molecules seen were clearly a combination of two “chunks” of literature molecules. In other words, a “molecular hybridisation” of literature compounds.
Tune in next time for a “Baran” spectacular and/or outline from the excellent panel discussion on success in academic careers.