Jun 1, 2023 11:12 PM
https://www.nature.com/articles/d41586-023-01735-1
EXCEPTS: Half a decade ago, chemist Mark Levin was a postdoc looking for a visionary project that could change his field. [...] one concept stood out: the ability to precisely edit a molecule by deleting, adding or swapping single atoms in its core.
[...] Levin is among a cadre of chemists pioneering these techniques, aiming to more efficiently forge new drugs, polymers and biological molecules such as peptides. In the past two years, more than 100 papers on the technique — known as skeletal editing — have been published, demonstrating its potential (see ‘Skeletal editing on the rise’). “There’s a tremendous amount of buzz right now around this topic,” says Danielle Schultz, director of discovery-process chemistry at pharmaceutical company Merck in Kenilworth, New Jersey.
To get a sense of the challenge, consider that the small, carbon-based molecules that make up most of the world’s drugs typically contain fewer than 100 atoms, and are assembled piece by piece in a series of chemical reactions. Some connect large sections of the molecule’s skeleton; others decorate that skeleton with clusters of atoms to create the final product. But few methods can reliably tweak a molecule’s core skeleton once it has been assembled. It’s a little like clipping together a house from Lego bricks: remodelling the exterior is trivial, but inserting a brick into the middle of a completed wall can’t be done without taking the house apart.
For organic chemists, the idea of being able to swap an atom in a molecule’s skeleton holds an intrinsic fascination. “It’s almost magical that these changes are now possible,” says Richmond Sarpong at the University of California, Berkeley, a leading light in skeletal editing.
But there’s also a very practical purpose. Drug discovery involves first finding a promising molecule, and then making hundreds of slightly different versions to try to improve potency or reduce toxicity. It’s relatively easy to change atomic groups on a molecule’s periphery to make variants. To edit the core, however, researchers typically must return to the start of their synthesis and make the modified skeleton from scratch. This is expensive, time-consuming and, in practice, heavily limits the variety of designs that drug firms screen and test. Reliable skeletal editing could massively speed up the process... (MORE - missing details)
EXCEPTS: Half a decade ago, chemist Mark Levin was a postdoc looking for a visionary project that could change his field. [...] one concept stood out: the ability to precisely edit a molecule by deleting, adding or swapping single atoms in its core.
[...] Levin is among a cadre of chemists pioneering these techniques, aiming to more efficiently forge new drugs, polymers and biological molecules such as peptides. In the past two years, more than 100 papers on the technique — known as skeletal editing — have been published, demonstrating its potential (see ‘Skeletal editing on the rise’). “There’s a tremendous amount of buzz right now around this topic,” says Danielle Schultz, director of discovery-process chemistry at pharmaceutical company Merck in Kenilworth, New Jersey.
To get a sense of the challenge, consider that the small, carbon-based molecules that make up most of the world’s drugs typically contain fewer than 100 atoms, and are assembled piece by piece in a series of chemical reactions. Some connect large sections of the molecule’s skeleton; others decorate that skeleton with clusters of atoms to create the final product. But few methods can reliably tweak a molecule’s core skeleton once it has been assembled. It’s a little like clipping together a house from Lego bricks: remodelling the exterior is trivial, but inserting a brick into the middle of a completed wall can’t be done without taking the house apart.
For organic chemists, the idea of being able to swap an atom in a molecule’s skeleton holds an intrinsic fascination. “It’s almost magical that these changes are now possible,” says Richmond Sarpong at the University of California, Berkeley, a leading light in skeletal editing.
But there’s also a very practical purpose. Drug discovery involves first finding a promising molecule, and then making hundreds of slightly different versions to try to improve potency or reduce toxicity. It’s relatively easy to change atomic groups on a molecule’s periphery to make variants. To edit the core, however, researchers typically must return to the start of their synthesis and make the modified skeleton from scratch. This is expensive, time-consuming and, in practice, heavily limits the variety of designs that drug firms screen and test. Reliable skeletal editing could massively speed up the process... (MORE - missing details)