ja8b11698_si_001.pdf (3.08 MB)
Complex Molecules That Fold Like Proteins Can Emerge Spontaneously
journal contribution
posted on 2018-12-18, 00:00 authored by Bin Liu, Charalampos G. Pappas, Ennio Zangrando, Nicola Demitri, Piotr J. Chmielewski, Sijbren OttoFolding 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.
History
Usage metrics
Categories
Keywords
self-synthesizing macrocyclic foldamerstructure drivesComplex Moleculesring sizesEmerge Spontaneouslyinterconverting moleculesnoncovalent interactionspeptide-nucleobase subunitsSingle-crystal X-ray crystallographysynthesiscombinatorial chemistryNMRcombinatorial chemistry approachdesign approachescomplexity
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC