Sequence-Selective Decapeptide Synthesis by the Parallel Operation of Two Artificial Molecular Machines

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Javier Echavarren
  • Malcolm Gall
  • Adrian Haertsch
  • Justin Spence
  • Daniel Tetlow
  • Chong Tian

Abstract

We report on the preparation of a decapeptide through the parallel operation of two rotaxane-based molecular machines. The synthesis proceeds in four stages: (1) simultaneous operation of two molecular peptide synthesizers in the same reaction vessel; (2) selective residue activation of short-oligomer intermediates; (3) ligation; (4) product release. Key features of the machine design include: (a) selective transformation of a thioproline building block to a cysteine (once it has been incorporated into a hexapeptide intermediate by one molecular machine); (b) a
macrocycle-peptide hydrazine linkage (as part of the second machine) to differentiate the intermediates and enable their directional ligation; and (c) incorporation of a Glu residue in the assembly module of one machine to enable release of the final product while simultaneously removing part of the assembly machinery from the product. The two molecular machines participate in the synthesis of a product that is beyond the capability of
individual small-molecule machines, in a manner reminiscent of the ligation and post-translational modification of proteins in biology.

Bibliographical metadata

Original languageEnglish
JournalAmerican Chemical Society. Journal
Publication statusAccepted/In press - 12 Mar 2021