Dynamic covalent self-assembly of mechanically interlocked molecules solely made from peptides.

TitleDynamic covalent self-assembly of mechanically interlocked molecules solely made from peptides.
Publication TypeJournal Article
Year of Publication2021
AuthorsSchröder, HV, Zhang, Y, A Link, J
JournalNat Chem
Volume13
Issue9
Pagination850-857
Date Published2021 09
ISSN1755-4349
KeywordsAmino Acid Sequence, Cysteine, Macromolecular Substances, Peptides, Protein Engineering
Abstract

<p>Mechanically interlocked molecules (MIMs), such as rotaxanes and catenanes, have captured the attention of chemists both from a synthetic perspective and because of their role as simple prototypes of molecular machines. Although examples exist in nature, most synthetic MIMs are made from artificial building blocks and assembled in organic solvents. The synthesis of MIMs from natural biomolecules remains highly challenging. Here, we report on a synthesis strategy for interlocked molecules solely made from peptides, that is, mechanically interlocked peptides (MIPs). Fully peptidic, cysteine-decorated building blocks were self-assembled in water to generate disulfide-bonded dynamic combinatorial libraries consisting of multiple different rotaxanes, catenanes and daisy chains as well as more exotic structures. Detailed NMR spectroscopy and mass spectrometry characterization of a [2]catenane comprising two peptide macrocycles revealed that this structure has rich conformational dynamics reminiscent of protein folding. Thus, MIPs can serve as a bridge between fully synthetic MIMs and those found in nature.</p>

DOI10.1038/s41557-021-00770-7
Alternate JournalNat Chem
PubMed ID34426684
PubMed Central IDPMC8446321
Grant ListR01 GM107036 / GM / NIGMS NIH HHS / United States