Effects of thionation and fluorination on cis-trans isomerization in tertiary amides: An investigation of N -alkylglycine (Peptoid) rotamers

Jens Engel-Andreasen, Kathrine Wich, Jonas S. Laursen, Pernille Harris, Christian Adam Olsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Peptoids constitute a class of peptidomimetics with potential as protease resistant, biologically active ligands. To harness the full potential of such compounds, however, detailed predictive insight into their propensity to adopt well-defined secondary structures is highly desirable. In this work we present an investigation of the effects of thioamides and/or fluorides in peptoid monomer model systems using chemical synthesis, NMR spectroscopy, and X-ray crystallography. We find that the steric environment surrounding the tertiary amide bonds is the key promoter of conformational preference, and X-ray crystallographic interrogation of our model systems did not suggest the presence of stabilizing n → π∗ interactions unless the carbonyls were altered electronically by α-halogenation or thioamide formation. In addition to the function as an investigative tool, these two types of modification may thus be utilized as stabilizers of secondary structure in future oligomer designs, such as the cis-amide-based polypeptoid helices that resemble the polyproline type-I helix.
Original languageEnglish
JournalJournal of Organic Chemistry
Volume80
Issue number11
Pages (from-to)5415-5427
Number of pages13
ISSN0022-3263
DOIs
Publication statusPublished - 2015

Keywords

  • Amides
  • Crystallography
  • Halogenation
  • Isomerization
  • Nuclear magnetic resonance spectroscopy
  • Biologically active ligands
  • Cis-trans Isomerization
  • Conformational preferences
  • Model system
  • Peptidomimetics
  • Poly prolines
  • Secondary structures
  • Tertiary amides
  • X ray crystallography

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