Oligo(N-aryl glycines): A new twist on structured peptoids

Neel H. Shah, Glenn L. Butterfoss, Khanh Nguyen, Barney Yoo, Richard Bonneau, Dallas L. Rabenstein, Kent Kirshenbaum

Research output: Contribution to journalArticle

Abstract

We explore strategies to enhance conformational ordering of N-substituted glycine peptoid oligomers. Peptoids bearing bulky N-alkyl side chains have previously been studied as important examples of biomimetic "foldamer" compounds, as they exhibit a capacity to populate helical structures featuring repeating cis-amide bonds. Substantial cis/trans amide bond isomerization, however, gives rise to conformational heterogeneity. Here, we report the use of N-aryl side chains as a tool to enforce the presence of trans-amide bonds, thereby engendering structural stability. Aniline derivatives and bromoacetic acid are used in the facile solid-phase synthesis of a diverse family of sequence-specific N-aryl glycine oligomers. Quantum mechanics calculations yield a detailed energy profile of the folding landscape and substantiate the hypothesis that the presence of anilide groups establishes a strong energetic preference for trans-amide bonds. X-ray crystallographic analysis and solution NMR studies verify this preference. Molecular modeling indicates that the linear oligomers can adopt helical structures resembling a polyproline type II helix. High resolution structures of macrocyclic oligomers incorporating both N-alkyl and N-aryl glycine units confirm the ability to direct the presence of trans-amide bonds specifically at N-aryl positions. These results are an important step in developing strategies for the rational de novo design of new structural motifs in biomimetic oligopeptoid systems.

Original languageEnglish (US)
Pages (from-to)16622-16632
Number of pages11
JournalJournal of the American Chemical Society
Volume130
Issue number49
DOIs
StatePublished - Dec 10 2008

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Peptoids
Amides
Glycine
Amino acids
Oligomers
Biomimetics
N-substituted Glycines
Bearings (structural)
Anilides
Solid-Phase Synthesis Techniques
Molecular modeling
Quantum theory
Aniline
Isomerization
Mechanics
Nuclear magnetic resonance
X-Rays
Derivatives
X rays
Acids

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Oligo(N-aryl glycines) : A new twist on structured peptoids. / Shah, Neel H.; Butterfoss, Glenn L.; Nguyen, Khanh; Yoo, Barney; Bonneau, Richard; Rabenstein, Dallas L.; Kirshenbaum, Kent.

In: Journal of the American Chemical Society, Vol. 130, No. 49, 10.12.2008, p. 16622-16632.

Research output: Contribution to journalArticle

Shah, Neel H. ; Butterfoss, Glenn L. ; Nguyen, Khanh ; Yoo, Barney ; Bonneau, Richard ; Rabenstein, Dallas L. ; Kirshenbaum, Kent. / Oligo(N-aryl glycines) : A new twist on structured peptoids. In: Journal of the American Chemical Society. 2008 ; Vol. 130, No. 49. pp. 16622-16632.
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