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Complex Molecules That Fold Like Proteins Can Emerge Spontaneously

[Image: see text] 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 architectu...

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Autores principales: Liu, Bin, Pappas, Charalampos G., Zangrando, Ennio, Demitri, Nicola, Chmielewski, Piotr J., Otto, Sijbren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356852/
https://www.ncbi.nlm.nih.gov/pubmed/30562021
http://dx.doi.org/10.1021/jacs.8b11698
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author Liu, Bin
Pappas, Charalampos G.
Zangrando, Ennio
Demitri, Nicola
Chmielewski, Piotr J.
Otto, Sijbren
author_facet Liu, Bin
Pappas, Charalampos G.
Zangrando, Ennio
Demitri, Nicola
Chmielewski, Piotr J.
Otto, Sijbren
author_sort Liu, Bin
collection PubMed
description [Image: see text] 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.
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spelling pubmed-63568522019-02-04 Complex Molecules That Fold Like Proteins Can Emerge Spontaneously Liu, Bin Pappas, Charalampos G. Zangrando, Ennio Demitri, Nicola Chmielewski, Piotr J. Otto, Sijbren J Am Chem Soc [Image: see text] 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. American Chemical Society 2018-12-18 2019-01-30 /pmc/articles/PMC6356852/ /pubmed/30562021 http://dx.doi.org/10.1021/jacs.8b11698 Text en Copyright © 2018 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Liu, Bin
Pappas, Charalampos G.
Zangrando, Ennio
Demitri, Nicola
Chmielewski, Piotr J.
Otto, Sijbren
Complex Molecules That Fold Like Proteins Can Emerge Spontaneously
title Complex Molecules That Fold Like Proteins Can Emerge Spontaneously
title_full Complex Molecules That Fold Like Proteins Can Emerge Spontaneously
title_fullStr Complex Molecules That Fold Like Proteins Can Emerge Spontaneously
title_full_unstemmed Complex Molecules That Fold Like Proteins Can Emerge Spontaneously
title_short Complex Molecules That Fold Like Proteins Can Emerge Spontaneously
title_sort complex molecules that fold like proteins can emerge spontaneously
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356852/
https://www.ncbi.nlm.nih.gov/pubmed/30562021
http://dx.doi.org/10.1021/jacs.8b11698
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