Conformationally Programmable Chiral Foldamers with Compact and Extended Domains Controlled by Monomer Structure

Zachariah Lockhart, Peter Knipe

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Foldamers are an important class of abiotic macromolecules, with potential therapeutic applications in the disruption of protein–protein interactions. The majority adopt a single conformational motif such as a helix. A class of foldamer is now introduced where the choice of heterocycle within each monomer, coupled with a strong conformation‐determining dipole repulsion effect, allows both helical and extended conformations to be selected. Combining these monomers into hetero‐oligomers enables highly controlled exploration of conformational space and projection of side‐chains along multiple vectors. The foldamers were rapidly constructed via an iterative deprotection‐cross‐coupling sequence, and their solid‐ and solution‐phase conformations were analysed by X‐ray crystallography and NMR and CD spectroscopy. These molecules may find applications in protein surface recognition where the interface does not involve canonical peptide secondary structures.
LanguageEnglish
Pages8478-8482
JournalAngewandte Chemie International Edition
Volume57
Issue number28
Early online date12 Jun 2018
DOIs
Publication statusPublished - 09 Jul 2018

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Conformations
Monomers
Proteins
X ray crystallography
Macromolecules
Oligomers
Peptides
Membrane Proteins
Nuclear magnetic resonance
Spectroscopy
Molecules

Keywords

  • conformational analysis
  • foldamers
  • oligomerization
  • protein-protein interactions

Cite this

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Conformationally Programmable Chiral Foldamers with Compact and Extended Domains Controlled by Monomer Structure. / Lockhart, Zachariah; Knipe, Peter.

In: Angewandte Chemie International Edition, Vol. 57, No. 28, 09.07.2018, p. 8478-8482.

Research output: Contribution to journalArticle

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