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.
Assigning enantiomers (mirror-image isomers of a compound, for the non-organic-chemists in the crowd) can be a pain. By definition, no non-chiral technique can tell the difference between such things, and many of the chiral techniques will just tell you that they’re different, but not which one is which. Take, for example, chiral chromatograp… Read More
Anyone who’s done fragment-based drug design (especially) or who has just looked at a lot of X-ray crystal structures of bound ligands will be able to back up this statement: if you sit down with a series of such structures, all bound to the same site, it is very, very difficult to rank-order them in… Read More
If you’re a chemist, then you like crystallization. I think that’s pretty much a given; I’ve never met anyone who doesn’t appreciate a good crystal, and watching them form out of a solution never stops feeling a bit like magic. When I was doing a project involving metal-organic frameworks, I had some of the best… Read More
Let’s think for a minute about what’s going on with tiny particles in solution, because we chemists spend an awful lot of time dealing with those. These particles vary in size from individual atoms all the way through small molecules, larger biomolecules and polymers, nanoscale engineered particles, micronized powders, etc., but the goo… Read More
Catalytically active proteins come in many varieties, and you can classify them in many ways. When you look closely at their structures, one such scheme might be the “solid” ones versus the “delicately balanced” ones. In the first category would be things like carbonic anhydrase or acetylcholinesterase: they do their jobs mo… Read More
Here’s another for the “things we just didn’t realize” file. This article is a nice look at “miniproteins” (also known as micropeptides), small but extremely important species that we’ve mostly missed out on due to both our equipment and our own biases in looking at the data. Other recent overviews are here… Read More
Kekulene! This is one of those molecules that someone who’s learning organic chemistry might sketch out on a whiteboard, wondering if it really exists. It does, but it’s not like we have a lot of recent information about it. There was a preparation of it in 1978 (from the Staab group at the Max-Planck Institute… Read More
At a previous company some years back, I was interested in getting a “covalent fragment” collection going, and did to a small extent. It got screened against some antibacterial targets, but never became all that popular. That was partly because fragment-based screening was a younger field, and combining it with covalent drug discovery … Read More
I remember the time before anyone did fragment-based drug discovery, when I heard high-micromolar binding ligands described as “carpet lint” or “stuff from the bottom of your shoe”. And you only heard then when the assays themselves even read out at that level, which certainly wasn’t a given. When I started, a suggesti… Read More
I’ve said this before, but if I had to pick one general feature of the current scientific literature versus that of (say) 30 years ago, I would vote for the ability to obtain data at far smaller scales (higher resolution) and the corresponding ability to more fully characterize structures and species that are far larger… Read More
