Chiral N-substituted glycines can form stable helical conformations.
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.
Armand
P
P
Chiron Corporation, Emeryville, CA 94608, USA.
Kirshenbaum
K
K
Falicov
A
A
Dunbrack
R L
RL
Dill
K A
KA
Zuckermann
R N
RN
Cohen
F E
FE
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
D009842:Oligopeptides; D034444:Peptoids; D005998:Glycine; D012521:Sarcosine