We discovered the mutaxanthenes via cluster activation using selection for antibiotic resistance and found a surprising labeling pattern during structural work. It is delightful to see this careful mechanistic study completing the mutaxanthene story!
*Comprehensive Structure–Activity Relationship Studies of Cepafungin Enabled by Biocatalytic C–H Oxidations*
*An NmrA-like enzyme-catalysed redox-mediated Diels–Alder cycloaddition with anti-selectivity*
A Diels–Alderase that catalyses the inherently disfavoured cycloaddition and forms a bicyclo[2.2.2]diazaoctane scaffold with a strict α-anti-selectivity has now been discovered. This Diels–Alderase, called CtdP, is an NmrA-like protein. Isotopic labelling, structural biology and computational studies reveal that the CtdP-catalysed Diels–Alder reaction involves a NADP+/NADPH-dependent redox mechanism.
*‘Disruptive’ science has declined — and no one knows why* (Nature 2023).
I find this summary and the research article it summarizes lacking some dimension on the theories of evolution of science. I did like their notion of a fixed ‘carrying capacity’ for highly disruptive science and technology. Analogously, there are also not more "disruptive" pop songs, or novels, or books of poetry, in fact they are probably declining per capita of the number of artists.
New Year‘s greetings for #chemtwitter & #ScienceTwitter followers, published on Jan 1st 🤷🏼♂️: „Rules were made to be broken“. 25 years since the Rule-of-5 was proposed: What is the relevance for today‘s small molecule drug discovery? @[email protected] @[email protected] https://www.nature.com/articles/s41570-022-00451-0
🐦🔗: https://twitter.com/HartungIngo/status/1609858708493766656
Twenty five years ago, Christopher Lipinski and colleagues published arguably the most influential sentence in small-molecule drug discovery. Their cleverly crafted ‘rule of 5’ (Ro5) mnemonic was adopted into everyday medicinal chemistry practice and has influenced a generation of small-molecule drug discovery scientists. Five times five years later, we consider the impact of the Ro5 and ask to what extent it should still guide today’s medicinal chemistry efforts.
Hello Mastodon, I'm a science journalist and chemistry writer, currently at C&EN. I'm trying to figure out this platform - any advice is greatly appreciated.
Referenced link: https://www.nature.com/articles/s41573-022-00615-z.epdf
Discuss on https://discu.eu/q/https://www.nature.com/articles/s41573-022-00615-z.epdf
Originally posted by Nature Portfolio / @[email protected]: https://twitter.com/NaturePortfolio/status/1604861383610449921#m
A Review in @NatRevDrugDisc discusses the mechanisms underlying resistance to targeted cancer therapies and assesses how these can be suppressed by using tailored combination therapies. https://www.nature.com/articles/s41573-022-00615-z.epdf
Over the past two decades, elucidation of the genetic defects that underlie cancer has resulted in a plethora of novel targeted cancer drugs. Although these agents can initially be highly effective, resistance to single-agent therapies remains a major challenge. Combining drugs can help avoid resistance, but the number of possible drug combinations vastly exceeds what can be tested clinically, both financially and in terms of patient availability. Rational drug combinations based on a deep understanding of the underlying molecular mechanisms associated with therapy resistance are potentially powerful in the treatment of cancer. Here, we discuss the mechanisms of resistance to targeted therapies and how effective drug combinations can be identified to combat resistance. The challenges in clinically developing these combinations and future perspectives are considered. Single-agent therapies targeting specific dysregulated pathways in cancer can be highly effective, but drug resistance frequently develops. Here, Bernards and colleagues discuss the mechanisms underlying resistance to targeted therapies, and assess how these can be suppressed by using tailored combination therapies.
Please spread the word.
Assistant Professor in Integrative structural biology with focus on structural dynamics
Stockholm
Deadline Dec 28.
https://www.su.se/english/about-the-university/work-at-su/available-jobs
Adam M Gilbert
Bethany Halford
Nature
Arne Elofsson