title: Chiral N-substituted glycines can form stable helical conformations.
abstract: BACKGROUND
  Short sequence-specific heteropolymers of N-substituted glycines (peptoids) have emerged as promising tools for drug discovery. Recent work on medium-length peptoids containing chiral centers in their sidechains has demonstrated the existence of stable chiral conformations in solution. In this report, we explore the conformational properties of these N alpha chiral peptoids by molecular mechanics calculations and we propose a model for the solution conformation of an octamer of (S)-N-(1-phenylethyl)glycine.
  
  
  RESULTS
  Molecular mechanics calculations indicate that the presence of N-substituents in which the N alpha carbons are chiral centers has a dramatic impact on the available backbone conformations. These results are supported by semi-empirical quantum mechanical calculations and coincide qualitatively with simple steric considerations. They suggest that an octamer of (S)-N-(1-phenylethyl)glycine should form a right-handed helix with cis amide bonds, similar to the polyproline type I helix. This model is consistent with circular dichorism studies of these molecules.
  
  
  CONCLUSIONS
  Peptoid oligomers containing chiral centers in their sidechains present a new structural paradigm that has promising implications for the design of stably folded molecules. We expect that their novel structure may provide a scaffold to create heteropolymers with useful functionality.
authors.affiliation: Chiron Corporation, Emeryville, CA 94608, USA.
authors.forename: P
authors.initials: P
authors.lastname: Armand
authors.forename: K
authors.initials: K
authors.lastname: Kirshenbaum
authors.forename: A
authors.initials: A
authors.lastname: Falicov
authors.forename: R L
authors.initials: RL
authors.lastname: Dunbrack
authors.forename: K A
authors.initials: KA
authors.lastname: Dill
authors.forename: R N
authors.initials: RN
authors.lastname: Zuckermann
authors.forename: F E
authors.initials: FE
authors.lastname: Cohen
mesh_terms: D019943:Amino Acid Substitution; D002942:Circular Dichroism; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D034444:Peptoids; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012521:Sarcosine / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D009842:Oligopeptides; D034444:Peptoids; D005998:Glycine; D012521:Sarcosine