Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer.
Modifying proteins with unnatural amino acids is a wide field with a lot of interesting research areas. Nature has provided us with twenty-odd amino acids (counting some rare ones), but there’s no reason that we have to play the hand that we’re dealt. Modifications of protein transcription and translation machinery have increasingly all… Read More
The 2018 Nobel Prize in Chemistry has gone to Frances Arnold (for directed evolution of enzymes) and to George Smith and Gregory Winter for phage display. These are worthy discoveries, techniques that have gone on to be used for a huge variety of work ranging from blue-sky research to marketed drugs, and the Nobel committee… Read More
You know that a technique has attained wide currency when the vendors start selling reagents and tools around it. Here’s an example in the protein degradation field: a team at Promega (well-known vendors of assay reagents and kits) report a new system to evaluate the extent and time course of protein degradation compounds. For those… Read More
I have always had a liking for the technique of having target proteins assemble their own inhibitors. This goes under several names: target-guided synthesis or protein-templated reactions more generally, and in situ click chemistry when the triazole/alkyne reaction is used as the assembly method. But the idea is the same in each case. You bring… Read More
Here’s a new piece by Stuart Schreiber that lays out a shift in thinking that many people in the chemical biology field have been experiencing over the last few years. Medicinal chemists are used to making functional drug candidates – and by “functional” I mean compounds that make protein targets do something. For an enzyme… Read More
I’ve written a few times about an odd sort of unnatural DNA sequence, where some of the nucleotides are connected via “click” triazole units rather than the traditional polyphosphate backbone. I remember wondering what the chemical biology community would make out of these things, and I wanted to report on at least one ingenious a… Read More
There’s a reagent used in chemical biology and protein labeling that should be getting a bit more attention than it does. Not because it’s useful – that’s already known – but because it can explode. Here’s the paper (from UC-Irvine and Amgen), and the compound is the 4-azido derivative of phenylalanine. Interest… Read More
Here’s a remarkable paper that shows how enzymes can be engineered to turn out some very unnatural-looking structures. Frances Arnold’s group at CalTech has published on a great deal of work in this area in the past, and this latest variation is something to see. They’ve been working with various heme proteins, since that reactive… Read More
Here’s an article in Nature Chemistry on organic synthesis and drug discovery, from a distinguished group of drug-industry chemists. The authors are going over a number of areas where medicinal chemistry could make use of more advanced synthetic techniques, and they’re good ones. For example, “From an industry perspective, the mos… Read More
Let’s think for a bit about how proteins bind to each other. After all, messing around with that is what keeps everyone in the drug industry employed, and the unmessed varieties of such binding events are what keep us all vertical and above room temperature, so it’s a worthy subject. The mental picture is of… Read More
