As the legend goes, people from Pfizer approached Phil Baran and told him “You know, we figured out what our problem is. We need more propellers on our molecules.” Phil said “OK, sounds like a good project” and put two grad students on it. Results: the 3-in-1 Science paper, with propellers spinning on every amine, SI, which is longer than my PhD thesis, and happy Pfizer counting cash.
By the way, Baran lab has a cold room for synthesis.
When you read a molecular biology textbook, it’s hard not to be amazed by the elegance and precision of cellular machinery. Everything is so logical, sequential, and organized to work properly. DNA templates self-copy and encodes RNA, which encodes proteins that do all kinds of work in a cell and organism. Francis Crick, who postulated this sequence, coined a term ‘the central dogma’ for it. And ever since ‘dogma’ became a buzzword for any fundamental assumption in molecular biology. But as with many assumptions in physics in the beginning of XX century, now many of these biological ‘dogmas’ are becoming obsolete. A recent review in Nuclear Acids Research discusses the premises for another dogma to fall. Continue reading “Short life of biological dogmas”
It’s really entertaining to watch the (over)reaction of Twitter on the controversial editorial in NEJM about data sharing and open science. As usual, it’s pretty hysteric but has a potential to cause some real-world consequences. The problem is that the authors were reckless enough to use term “research parasites” for those scientists who use the data from other labs without conducting their own experiments. Continue reading “Research parasites”
There’s a scandal growing in the field of CRISPR due to a lawsuit and patent war between pioneers of the technology. And then this paper in Cell appeared and made the things worse… I don’t want do discuss in details the story behind, because there are plenty of better information sources all over the internet. What I want to bring up today is the problem of communication in the highest level of science, among respected professors.
Today we know whole lot about different receptors in our body. Often we know which one to target for particular disease and how the drug molecules operate on the molecular level. But it’s always interesting to learn something new about how do we sense the world around us. What molecules make us aware of sight, taste, smell, hearing and touch? The paper in the latest issue of PNAS gives some new insights in the perception of sour taste. Continue reading “Sour-tasting mechanism”
Another great reaction that I was thinking to dedicate a separate post for but will never manage. Just check out this teaser scheme: two steps, two distant stereocenters, great chemoselectivity, and so drug-like!
Brilliant batch-washing of NMR tubes in a vacuum dessicator that has already got some good publicity in the blogosphere but probably won’t get too many citations. In theory, nothing can stop you from applying the same technique to any other glassware that has a solid bottom (flasks, beakers, etc.).
Today I just wanted to highlight a great post on one of the core difference between academic and industrial labs, namely diligence in writing down detailed standard operation procedures (SOPs).
Coming from my PhD lab with the organic chemistry background, I have never realized the importance of this. After all, the synthetic techniques didn’t change too much for centuries and it shouldn’t matter, how you heat and steer your stuff in a round-bottom flask, right? Wrong! There are plenty of opportunities to reproducibly screw up your reaction, equipment or health when doing even the simplest operations like heating and cooling wrongly.
In the chemical biology lab the importance of SOPs is on the whole new level because the number of moving parts is so much larger than in synthesis. And yet, the best practices are mostly passed as folklore, from mouth to mouth, and never get written down properly.
I’m not saying that one absolutely needs to keep track of batch numbers of purchased reagents and material of gloves used for a particular operations (although it also may save your life sometimes). But I’m pretty sure that emphasizing importance of SOPs will improve reproducibility and expertise transfer inside any lab. And this ultimately will lead to better science.
Discovery and development of Pd-catalyzed cross-coupling reactions greatly spurred the rise of medicinal chemistry. They also strongly biased the chemical space of potential drugs to biaryl-like compounds. Currently, directed by growing demand for chemical diversity, the field is evolving in the direction of more flexible chemotypes, where rigid scaffolds are connected via single Csp3-Csp3 bonds.
Today chemical biology generates new high-throughput methods of studying biomolecules almost as quickly as organic chemists report total syntheses. Whole genome, transcriptome, proteome, lipidome, glycome etc. analyses are flourishing and delivering vast amounts of data. Bioinformaticist are trying to cope with the data flow by archiving them in various databases. This has led to a situation when the number and diversity of databases became incomprehensible for a human being. Continue reading “The database of databases”
Epigenetics is an exciting but a weird area. It’s well recognized that messing with chromatin and chemical modifications of nucleic acids has profound consequences at the cellular and organism levels. But for me the mechanistic rationale for targeting epigenome pharmacologically was always somewhere close to throwing a monkey wrench into the clockworks and watching what will happen. It seems (not surprisingly) that in fact the effects are more predictable. Continue reading “Epigenetic ant reprogramming”