Synthesising small molecular machines has been somewhat limited to making molecules that can walk or spin round cogwheels. Mind you that is still pretty impressive. Now things are set to change with a recent publication in Science by Dr Leigh from the University of Manchester in the UK.
The Manchester group synthesised a rotaxane (a molecular ring) threaded through an axle that consists of peptides. The rotaxane has a thiolate moiety that removes the amino acids in sequence and transfers them to the site of the new growing peptide chain. There is a wonderful summary in C&E News, with an interesting video of how it all works.
The group used 1018 machines in parallel to generate milligram quantities of a single sequence peptide. This mimics the ribosome in its valuable function in the generation of peptides. The “arm” picks up the amino acid by a transacylation reaction and delivers them to a different place on the ring.
There are still some problems to be solved, for example the rather slow reaction rate as the ring needs about 12 hours to make the amide bonds. Compare this to the 15-20 bonds per second produced by the ribosome itself. There are a few other problems, and no doubt they are being addressed at this moment. However this paper and the technology are impressive and will probably have a great future.
Imagine what several moles of these could do once things become optimised, producing peptides of any sequence one desired, natural or unnatural. This is a fascinating concept and I look forward to seeing lots more appearing on this system.
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