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. Synthesis of MIMs from natural biomolecules remains highly challenging. Here we report on a synthesis strategy for interlocked molecules solely made from peptides—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 comprised of 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.
Lasso peptides are a family of ribosomally
synthesized and post-translationally
modified peptides (RiPPs) defined by their threaded structure. Besides
the class-defining isopeptide bond, other post-translational modifications
(PTMs) that further tailor lasso peptides have been previously reported.
Using genome mining tools, we identified a subset of lasso peptide
biosynthetic gene clusters (BGCs) that are colocalized with genes
encoding protein l-isoaspartyl methyltransferase (PIMT) homologues.
PIMTs have an important role in protein repair, restoring isoaspartate
residues formed from asparagine deamidation to aspartate. Here we
report a new function for PIMT enzymes in the post-translational modification
of lasso peptides. The PIMTs associated with lasso peptide BGCs first
methylate an l-aspartate side chain found within the ring
of the lasso peptide. The methyl ester is then converted into a stable
aspartimide moiety, endowing the lasso peptide ring with rigidity
relative to its unmodified counterpart. We describe the heterologous
expression and structural characterization of two examples of aspartimide-modified
lasso peptides from thermophilic Gram-positive bacteria. The lasso
peptide cellulonodin-2 is encoded in the genome of actinobacterium Thermobifida cellulosilytica, while lihuanodin is encoded
in the genome of firmicute Lihuaxuella thermophila. Additional genome mining revealed PIMT-containing lasso peptide
BGCs in 48 organisms. In addition to heterologous expression, we have
reconstituted PIMT-mediated aspartimide formation in vitro, showing
that lasso peptide-associated PIMTs transfer methyl groups very rapidly
as compared to canonical PIMTs. Furthermore, in stark contrast to
other characterized lasso peptide PTMs, the methyltransferase functions
only on lassoed substrates.
Donor-acceptor materials with small HOMO-LUMO gaps are important in molecular electronics, but are often difficult to synthesise. A simple and efficient way to position tetrathiafulvalene (TTF) as the donor and naphthalene diamide (NDI) as the acceptor in close proximity to each other in a divalent crown/ammonium pseudo[2]rotaxane is presented. The divalent design provides high chelate cooperativity and much stronger binding compared with a monovalent analogue. The pseudo[2]rotaxane was then doubly interlocked by stoppering it in a catalyst-free 1,3-dipolar cycloaddition. UV/Vis and cyclic voltammetry experiments with the resulting [2]rotaxane revealed the optoelectronic properties of an intramolecular charge transfer with a small HOMO-LUMO energy gap. Redox-switching experiments showed the rotaxane to be pentastable. DFT calculations provided insights into the electronic structures of the five redox states.
Reversible redox-switching of a planar chiral [2]rotaxane with a tetrathiafulvalene-bearing crown ether macrocycle generates a complete sign reversal of the main band in the ECD spectrum, as shown by experiment and rationalised by DFT calculations.
We report the first POC, containing perfluorinated aromatic panels forming quickly and in high purity, despite low preorganization encoded in the starting materials.
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