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Organic chemistry
The addition of a methyl group to a drug molecule can greatly alter the drug's pharmacological properties. A catalyst has been developed that enables this 'magic methyl effect' to be rapidly explored for drug discovery. See p.621
Developing a small-molecule drug requires iterations of building and testing new compounds to find one that strikes the right balance of pharmacological properties. The process typically takes more than 10 years and costs billions of dollars, because, for every 5,000 compounds made and tested, only one will become an approved drug12. Indeed, a highschool basketball player is twice as likely to end up playing in the US professional league as any single compound tested in a drug-discovery programme is to become a marketed drug (see go.nature.com/2v8pnfm). One approach to accelerating drug discovery is late-stage functionalization, in which previously prepared test compounds are decorated with new atoms in the hope of favourably adjusting their pharmacological properties. On page 621, Feng et at.3 report an outstanding advance towards this long-standing and historically challenging strategy.
Introducing just one cluster of atoms (a functional group) into a drug molecule can drastically alter the molecule's properties. For instance, adding a methyl group (CH3, one of the smallest functional groups) can enhance a compound's binding affinity for its biological target more than 1,000-fold, a phenomenon termed4 the 'magic methyl effect'. This is because the installation of a methyl group alters the shape of the molecule such that it can readily nestle inside a targeted protein's active site, akin to how an ergonomic computer mouse fits snugly in the palm of your hand.
However, making even small adjustments to molecules is frequently a major undertaking, one that effectively requires chemists to break apart the entire structure and reassemble a dozen or more smaller pieces for each change. Imagine how much time and money it would cost if adding a new window to your home required the entire house to be taken apart and rebuilt from scratch. Chemists working in...