- by Derek LoweNow that I'm back (from some traveling) it looks like the first item of business is the advent of AlphaFold 3. That Nature preprint (which is open access) says that this extends the predictive powers of the software to other classes of molecules and to complexes between them. I had expressed some skepticism in the past about how easy that would be to do in the case of small synthetic molecules – y'know, drug candidates – and I am very […]
- by Derek LoweI've been meaning to blog about this paper from a large team at Chugai, looking at ways to make rather large cyclic peptide structures that can also still be drugs. The whole "peptides as drugs" topic has been a perennial here on the blog, and by that I mean "going back to 2002", with updates along the way. Here's a recent review on the subject (and there are plenty more out there!) The reasons it's such a focus in drug […]
- by Derek LoweThe Biden administration has made headlines with a roadmap document suggesting the use of "march-in" rights regarding drug patents. And that should get some attention: this provision of the 1980 Bayh-Dole Act has never been used, and it would be a huge change in the way that the pharmaceutical industry is regulated in the US. It's a big topic, and I've broken it down into sections: Part One: The Law Itself Here is the actual text of the law regarding […]
- by Derek LoweI wanted to take a moment to note the 100th volume of Organic Syntheses, because that series is a part of every organic chemist's scientific upbringing. For those outside the field, "Org Syn" is a series of annual volumes that details the preparation of interesting and useful compounds (and/or demonstrates useful new reaction techniques). The distinguishing factors are that these preparations are given in great detail, with attention to reaction variables that can affect the yield and purity of the […]
- by Derek LoweSince many readers here (and my own household as well) are heading into the holiday season, it's time for something I like to do on this site: lab preparations that you can eat! Here are all the recipes posted over the years. Today's is an Ina Garten recipe that we've made many times here. You'll need a whole chicken (3 to 4 lbs, 1.4-1.8 kg) and a good knife or pair of kitchen shears to prepare it, along with lemon […]
- by Derek LoweOK, this is not exactly traditional Christmastime Mexican food (that would be tamales, made by someone's grandmother), but it's a nice dish and we just made another batch of these around here last night. You'll need some large chile peppers, four of them for the recipe quantities to follow. I use the dark green and glossy Poblanos, whose width makes the preparation easier, but there's no reason other similarly-shaped peppers wouldn't work). Poblanos are generally pretty mild, with some green […]
- by Derek LoweThis is a modified and modifiable version of the recipe that Fuschia Dunlop gives in her book Land of Plenty on Sichuan cooking. That's an excellent resource, as are Dunlop's other works on Chinese cooking, because she has lived and traveled extensively in the country with a keen eye for the food, how it's prepared and served, and the history behind it. You can learn a lot of interesting and unusual things just by reading through her cookbooks, but it's […]
- by Derek LowePost holiday season (and after three recipe posts in a row!) it might be a good time to take a look at the situation with semaglutide (Ozempic, Wegovy). It has of course leapt up the charts of most-prescribed drugs since its effects on weight loss have become clear in clinical trials, but demand has been outstripping supply, with some interesting consequences. Novo Nordisk was able to handle the market when it was primarily a drug in diabetes therapy, but that […]
- by Derek LoweHere's a strange and unexpected bit of biology, but considered where it's coming from, perhaps strange stuff is to be expected? This is a paper on a type of "giant virus", a class that has only started coming into focus in recent years. The first such were described back in the early 1980s, but more of them were found in the 1990s, and in the last twenty years it's become apparent that this is a whole virus type that had […]
- by Derek LoweJanuary is traditionally the time when gyms are busiest, as people try to get a start on a new year by getting more exercise (and perhaps to also try to deal with the more immediate effects of the holiday season!) There's been a great deal of work put into figuring out the cellular and biochemical mechanisms of exercise and its benefits – that's bound to be a complex story, and the possible interactions of exercise with commonly taken metabolic drugs […]
- by Derek LoweI wrote a year ago about evidence for a connection between Epstein-Barr virus (EBV) and multiple sclerosis. Since then, I’m glad to report that the evidence has become even stronger. The first new advance was the discovery of a region of an EBV protein (EBNA1) that could well be the site of the problem. Antibodies that are raised to the 386-405 part of the EBNA1 protein also recognize a particular epitope (amino acids 370-385) of a protein in human glial […]
- by Derek LoweI wrote here a couple of times last year about reports of unusual chemical behavior in water microdroplets. Those posts will send you to a number of references, and there are plenty more out there. One explanation has been that such species may have extremely high electric fields at their surfaces, and it's for sure that (1) the actual surface of bulk water is a very different environment than the interior, and (2) microcroplet are a long way from being […]
- by Derek LoweHere's a recent paper from Rick Young's group and co-workers on the chemical environment in biochemical condensate droplets. It's been assumed that these things, which come in a number of varieties, to judge from the sequences of the proteins likely to form them, must have a similar variety of solvation properties inside them. Many biomolecular condensates seem to be "complex coacervates", mixtures of net-positively charged proteins and net-negatively-charged RNA species or other proteins, but others seem to be driven by […]
- by Derek LoweThe updates to things I've been writing about here are coming almost too quickly to catch up with, especially since I try to vary the subject matter here day by day (on the theory that if someone stops by and finds that they're not interested in today's post, that they have a good chance of finding something totally different the next time). But early this week I was writing on the latest developments in the developing story of whether multiple […]
- by Derek LoweSince I was mentioning engineered cyclic peptides as drug candidates the other day, this report (in the form of two papers) is pretty timely. It's about a new antibiotic candidate (Zosurabalpin, RO7075573) and its unusual mechanism of action against some Gram-negative bacteria. Now, anything that is a potential new weapon against those guys has my respect, because I've tried my hand at them personally and they are resilient beasts. Compared to mammalian cells, they are covered in futuristic reactive combat […]
- by Derek LoweHere's a paper on an outside-the-usual topic, one that comes up in these days of modern times (as the Firesign Theater used to say), by which I mean our ability to do useful work at smaller and smaller physical scales. The authors are looking at the use of glass nanopipettes as samplers for analytical techniques, which is not a new idea, of course, but they're among the many groups who are trying to improve the signal/noise. Fundamentally, you'd want to […]
- by Derek LoweWhen we last visited the lively, ever-evolving world of shady scientific publishing, we saw publication brokers offering journal editors kickbacks to push their papers into print, and here's plenty more about it in a new article here at Science. I particularly enjoy the parts where some of these sleazeballs wake up to the fact that they are not talking to customers, but rather to a reporter, and suddenly their entire demeanour changes. Those customers are both on the author side […]
- by Derek LoweThis recent preprint is of interest as the application of AlphaFold/RoseTTAFold-type technology continue to expand. One of the big frontiers is their application to the interactions of small molecules with protein binding pockets, and so far results have been mixed. But that's not always (or even often) the fault of the software or the approach. The protein-prediction algorithms are of course built from the large corpus of experimentally determined protein structures, an extensive (and extensively curated) reservoir of ground truth. […]
- by Derek LoweI had an email from one of the authors on this new preprint from the Baran group, which describes the synthesis of several dragocins. These are bizarre marine natural products, and their synthesis uses a neat electrochemical cyclization to form the central nine-membered ring. You can think of some other ways to close that one when you look at those structures, but by gosh, those turn out not to work (which is how natural products synthetic plans tend to go!) […]
- by Dere LoweI was just ranting about the state of the scientific literature the other day, what with the news of ever-increasing offers of bribes to journals and their editorial staffs to publish paper-mill manuscripts. And while I stand by those opinions (and how), it's important to remember that contaminated publications aren't just a problem in a bunch of obscure journals from a bunch of Chinese military hospitals and obscure regional medical universities that you've never heard of. No, while those are […]
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