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.
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
Here’s more evidence of the power of the MicroED electron diffraction technique: this new paper reports the structure of two reactive organometallic species whose structures could not be determined by either NMR methods or conventional X-ray crystallography. One of them is the zirconium hydride species known as Schwartz’s reagent (zirco… Read More
Here’s a neat paper that’s shown up on arXiv.org on protein structures. The authors, from Yale and Edinburgh, are specifically comparing X-ray crystallographic structures with NMR-determined ones in solution. It’s widely known that when you look at the same (or nearly the same) proteins by both those methods that you see small but… Read More
OK, let’s get reductionist, and let’s see why getting reductionist often works so well. How do you know when your finger has touched something? You feel it – but how do you feel it? Your nerves have sent an impulse to your brain, which interprets it as something having physically come into contact with your… Read More
