Sequence-Specific β-Peptide Synthesis by a Rotaxane-Based Molecular Machine.
Guillaume De BoMalcolm A Y GallMatthew O KitchingSonja KuschelDavid A LeighDaniel J TetlowJohn W WardPublished in: Journal of the American Chemical Society (2017)
We report on the synthesis and operation of a three-barrier, rotaxane-based, artificial molecular machine capable of sequence-specific β-homo (β3) peptide synthesis. The machine utilizes nonproteinogenic β3-amino acids, a class of amino acids not generally accepted by the ribosome, particularly consecutively. Successful operation of the machine via native chemical ligation (NCL) demonstrates that even challenging 15- and 19-membered ligation transition states are suitable for information translation using this artificial molecular machine. The peptide-bond-forming catalyst region can be removed from the transcribed peptide by peptidases, artificial and biomachines working in concert to generate a product that cannot be made by either machine alone.