10.1021/jacs.8b11698.s001
Bin Liu
Bin
Liu
Charalampos G. Pappas
Charalampos G.
Pappas
Ennio Zangrando
Ennio
Zangrando
Nicola Demitri
Nicola
Demitri
Piotr J. Chmielewski
Piotr J.
Chmielewski
Sijbren Otto
Sijbren
Otto
Complex
Molecules That Fold Like Proteins Can Emerge
Spontaneously
American Chemical Society
2018
self-synthesizing macrocyclic foldamer
structure drives
Complex Molecules
ring sizes
Emerge Spontaneously
interconverting molecules
noncovalent interactions
peptide-nucleobase subunits
Single-crystal X-ray crystallography
synthesis
combinatorial chemistry
NMR
combinatorial chemistry approach
design approaches
complexity
2018-12-18 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Complex_Molecules_That_Fold_Like_Proteins_Can_Emerge_Spontaneously/7594235
Folding can bestow
macromolecules with various properties, as evident
from nature’s proteins. Until now complex folded molecules
are the product either of evolution or of an elaborate process of
design and synthesis. We now show that molecules that fold in a well-defined
architecture of substantial complexity can emerge autonomously and
selectively from a simple precursor. Specifically, we have identified
a self-synthesizing macrocyclic foldamer with a complex and unprecedented
secondary and tertiary structure that constructs itself highly selectively
from 15 identical peptide-nucleobase subunits, using a dynamic combinatorial
chemistry approach. Folding of the structure drives its synthesis
in 95% yield from a mixture of interconverting molecules of different
ring sizes in a one-step process. Single-crystal X-ray crystallography
and NMR reveal a folding pattern based on an intricate network of
noncovalent interactions involving residues spaced apart widely in
the linear sequence. These results establish dynamic combinatorial
chemistry as a powerful approach to developing synthetic molecules
with folding motifs of a complexity that goes well beyond that accessible
with current design approaches. The fact that such molecules can form
autonomously implies that they may have played a role in the origin
of life at earlier stages than previously thought possible.