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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ASJC Scopus subject areas

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

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