- by I've written before here about "magic methyl" groups, the effect that you see sometimes in med-chem where the addition of a single methyl group changes a compound's activity profoundly. That's one of the things that can make structure-activity exploration such a fraught business, because you really do never quite know what's going to happen. At one point in my career, I worked on three projects in a row where the lead compound (at least for a good part of the […]
- by Respiratory Syncytial Virus (RSV) is a major public health issue, but its damage is concentrated at the two ends of the age spectrum: infants and older adults. It's a common virus for all ages, but once out of early childhood the symptoms are much less severe for adolescents and adults (because they've been almost always infected before as children!) But in the elderly population it can and does cause trouble again and can lead to outright pneumonia, which is in […]
- by This is a neat application of mRNA vaccine technology from researchers at Penn and the Children's Hospital of Philadelphia that might address a pretty widespread bacterial problem. Significant disruptions of the human gut microbiome, through disease or through antibiotic treatment can lead to a very unwelcome new status quo in the intestine: a takeover by the bacterium Clostridioides difficile, known to its (many) non-admirers as "C diff". It's a Gram-positive anaerobe that is found in small populations even in healthy […]
- by I have written about Cassava Sciences several times on this blog over the years, most recently here. The short summary is that they are a small biotech with a new mechanism of action for Alzheimer's and other neurodegenerative disorders, one that came out of work at a lab at CUNY some years ago. So far that doesn't sound so bad, does it? We need new ideas in that field, and academia is where a great many of those ideas come […]
- by It's the day before Thanksgiving here in the US, which means that (as longtime readers know) I will be preparing a chocolate pecan pie, as I do every year. The recipe is here, and I've been making it the same way for nearly thirty years, so I think I can put this one in the "reliable" category. That's it at right! I'm also in charge of preparing the turkey around here – the menu is (pretty much as always) said […]
- by Anyone doing chemical biology work rapidly becomes familiar with what I'll call the Tagger's Paradox, after the quantum mechanical observer's paradox. That one is of course the problem that so many things that allow you to observe the behavior of tiny quantum-mechanics-driven systems can also end up perturbing them. Social scientists have a similar problem – telling people that they're part of a study to observe how they behave will inevitably change their behaviors. Here's our problem, then: when you're […]
- by This new paper is the sort of thing that you don't see all that often, although perhaps we should. The authors are working in the (ever-larger) field of bifunctional molecules, and among the many examples of these in the literature are species called (by their discoverers) ATTECs, for autophagosome-tethering compounds. Instead of calling in the ubiquitination/proteasome machinery to degrade a target (as the by-now-well-known PROTAC molecules do), these are meant to engage another cellular clearance pathway, autophagy. That one's a […]
- by I've written here many times about disordered proteins, those floppy fuzzballs that have outsized role in living cells. Here's an early post, and more are linked below. Their actions can be a challenge to a guy like me, merely a poor chemist from the hinterlands, because instead of having defined stuctures – folds and pockets like any normal protein – they (as the name implies) have no defined structure at all. There's not a good macroscale analogy handy to help […]
- by I've long had a fondness for medium-sized heterocyclic rings (seven, eight, nine-membered ones), because there just aren't that many of them around compared to the ubiquitous five- and six-membered ones. There are some good reasons for this, and the biggest is that rings of these sizes are harder to form than the smaller ones (or the larger ones, too, perversely). A lot of study has gone into this topic, with Jack Baldwin's "Rules for Ring Closure" as a comparatively early […]
- by Earlier this year there was news about a new docking program for fitting small molecule ligands into proteins that used diffusion-based methods. DiffDock made a splash, and there was no small amount of hype around it – for example, that press release linked in the first sentence says that "The model's unique approach to computational drug design is a paradigm shift from current state-of-the-art tools that most pharmaceutical companies use, presenting a major opportunity for an overhaul of the traditional […]
- by In our last exciting installment, the BioSecure Act (which would prevent Federal agencies from doing business with a number of Chinese biopharma service companies) had passed in the House of Representatives and moved on to the Senate. And there it has run into some dead ends. The latest news is that the bill's language was not included in a big must-pass defense omnibus bill (the US National Defense Authorization Act), which is the route that many thought it could take […]
- by I hadn't seen this preprint until this Nature piece called my attention to it, but it's certainly worth a look. The authors have gone back over the recent biology literature (3387 articles from 2023 in 15 high-profile journals) and they find that 88% of these use some sort of bar graph to present data. And I can well believe it! But unfortunately, about a third of those have presentation mistakes in them. The two most common mistakes are (1) not […]
- by I was at the bench yesterday afternoon (yep, I still have a hood, and I still make some compounds – mostly weird stuff that I would feel bad asking someone else to spend time making!) And while isolating and purifying a couple of new probes, it occurred to me that there are a lot of muscle-memory tasks that I've built up over the years that are nearly unconscious for me by now. That shouldn't be a surprise, I guess – […]
- by Some years ago I spent time working in the nuclear receptor field, specifically the PPAR subtypes. It's a complex area, as we all discovered (there were a number of companies working in it at the time), and one of the lessons that I took away very quickly was that whoever imported the GPCR terms "agonist" and "antagonist" into the nuclear receptor field should be tarred and feathered. Those are useful terms for G-protein coupled receptors, although there are complications in […]
- by I wanted to highlight a couple of papers that illustrate the long-running world conquest of mass spectrometry methods (and I for one have long welcomed our mass spec overlords). The number of useful variations that can be worked on this technique is a continual source of amazement, and there's no reason to think that it will stop any time soon. Both of the papers mentioned today are aiming at analyzing a large number of chemical reactions simultaneously, with the goal […]
- by This is another one of those tales that could only be told with the advent of modern analytical methods, for sure. I've written about micro-electron diffraction several times on the site, and that's the starting point for this work. In traditional diffraction methods for solving the structures of crystalline compounds, you of course use X-rays instead, an idea that is over 100 years old and earned Max von Laue a well-deserved Nobel. He and Peter Ewald (also a founding father […]
- by Biology as we find it is full of Chesterton's Fence situations. That's an analogy that gets trotted out in a lot of political and regulatory situations, but we're dealing with it because we have arrive to sentience and technological agency after several billion years of evolution. I.e., the party has been going on for quite a while before we walked in the door. There's no better way to explain the idea than to go to the man himself, since G. […]
- by People outside of drug discovery are often quite surprised to find out how little we know about what happens to our compounds once they get into cells. It's a hard problem, though – the quantities are small, and the compounds don't have any particular handles on them to let you see them or track them. And of course the cellular environment is complex, to put it mildly. The cytoplasm itself is a near-gelatinous mixture of thousands of components, and there […]
- by You get widely varied perspective on targeted cancer therapeutics depending on where you get your information from. Cancer therapy centers in the US like to advertise as if they can zero right in on a particular patient's particular sort of cancer and then reach up on the shelves to pick out which of the thousands of alternatives will be most efficacious. Now it's true that we can do more of that than we used to, but the real-world situation is […]
- by We go through a lot of pickles around here – my wife and I, and both of our kids when they're here. They grew up that way, and regard their occasional contacts with people who dislike pickles (or are just indifferent to them) with puzzlement and pity. We always have store-bought ones around, but the fridge generally has home-made varieties in it, and I thought I'd pass some of those along. These range from "Extremely easy, nay, downright cheating" all […]
Mass spectrometry websites, social media, journal feeds, and other links and items of interest to the mass spectrometry community.
