Structural and Spectroscopic Studies of Peptoid Oligomers with α-Chiral Aliphatic Side Chains

Cindy W. Wu, Kent Kirshenbaum, Tracy J. Sanborn, James A. Patch, Kai Huang, Ken A. Dill, Ronald N. Zuckermann, Annelise E. Barron

Research output: Contribution to journalArticle

Abstract

Substantial progress has been made in the synthesis and characterization of various oligomeric molecules capable of autonomous folding to well-defined, repetitive secondary structures. It is now possible to investigate sequence-structure relationships and the driving forces for folding in these systems. Here, we present detailed analysis by X-ray crystallography, NMR, and circular dichroism (CD) of the helical structures formed by N-substituted glycine (or "peptoid") oligomers with α-chiral, aliphatic side chains. The X-ray crystal structure of a N-(1-cyclohexylethyl)glycine pentamer, the first reported for any peptoid, shows a helix with cis-amide bonds, ∼3 residues per turn, and a pitch of ∼6.7 Å. The backbone dihedral angles of this pentamer are similar to those of a polyproline type I peptide helix, in agreement with prior modeling predictions. This crystal structure likely represents the major solution conformers, since the CD spectra of analogous peptoid hexamers, dodecamers, and pentadecamers, composed entirely of either (S)-N-(1-cyclohexylethyl)glycine or (S)-N-(sec-butyl)glycine monomers, also have features similar to those of the polyproline type I helix. Furthermore, this crystal structure is similar to a solution NMR structure previously described for a peptoid pentamer comprised of chiral, aromatic side chains, which suggests that peptoids containing either aromatic or aliphatic α-chiral side chains adopt fundamentally similar helical structures in solution, despite distinct CD spectra. The elucidation of detailed structural information for peptoid helices with α-chiral aliphatic side chains will facilitate the mimicry of biomolecules, such as transmembrane protein domains, in a distinctly stable form.

Original languageEnglish (US)
Pages (from-to)13525-13530
Number of pages6
JournalJournal of the American Chemical Society
Volume125
Issue number44
DOIs
StatePublished - Nov 5 2003

Fingerprint

Peptoids
Oligomers
Amino acids
Dichroism
Circular Dichroism
Glycine
Crystal structure
N-substituted Glycines
Nuclear magnetic resonance
X ray crystallography
X Ray Crystallography
Biomolecules
Dihedral angle
Amides
Peptides
Monomers
X-Rays
Proteins
X rays
Molecules

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Structural and Spectroscopic Studies of Peptoid Oligomers with α-Chiral Aliphatic Side Chains. / Wu, Cindy W.; Kirshenbaum, Kent; Sanborn, Tracy J.; Patch, James A.; Huang, Kai; Dill, Ken A.; Zuckermann, Ronald N.; Barron, Annelise E.

In: Journal of the American Chemical Society, Vol. 125, No. 44, 05.11.2003, p. 13525-13530.

Research output: Contribution to journalArticle

Wu, CW, Kirshenbaum, K, Sanborn, TJ, Patch, JA, Huang, K, Dill, KA, Zuckermann, RN & Barron, AE 2003, 'Structural and Spectroscopic Studies of Peptoid Oligomers with α-Chiral Aliphatic Side Chains', Journal of the American Chemical Society, vol. 125, no. 44, pp. 13525-13530. https://doi.org/10.1021/ja037540r
Wu, Cindy W. ; Kirshenbaum, Kent ; Sanborn, Tracy J. ; Patch, James A. ; Huang, Kai ; Dill, Ken A. ; Zuckermann, Ronald N. ; Barron, Annelise E. / Structural and Spectroscopic Studies of Peptoid Oligomers with α-Chiral Aliphatic Side Chains. In: Journal of the American Chemical Society. 2003 ; Vol. 125, No. 44. pp. 13525-13530.
@article{2999e90ffdf744f0bb3a16f189f57d2c,
title = "Structural and Spectroscopic Studies of Peptoid Oligomers with α-Chiral Aliphatic Side Chains",
abstract = "Substantial progress has been made in the synthesis and characterization of various oligomeric molecules capable of autonomous folding to well-defined, repetitive secondary structures. It is now possible to investigate sequence-structure relationships and the driving forces for folding in these systems. Here, we present detailed analysis by X-ray crystallography, NMR, and circular dichroism (CD) of the helical structures formed by N-substituted glycine (or {"}peptoid{"}) oligomers with α-chiral, aliphatic side chains. The X-ray crystal structure of a N-(1-cyclohexylethyl)glycine pentamer, the first reported for any peptoid, shows a helix with cis-amide bonds, ∼3 residues per turn, and a pitch of ∼6.7 {\AA}. The backbone dihedral angles of this pentamer are similar to those of a polyproline type I peptide helix, in agreement with prior modeling predictions. This crystal structure likely represents the major solution conformers, since the CD spectra of analogous peptoid hexamers, dodecamers, and pentadecamers, composed entirely of either (S)-N-(1-cyclohexylethyl)glycine or (S)-N-(sec-butyl)glycine monomers, also have features similar to those of the polyproline type I helix. Furthermore, this crystal structure is similar to a solution NMR structure previously described for a peptoid pentamer comprised of chiral, aromatic side chains, which suggests that peptoids containing either aromatic or aliphatic α-chiral side chains adopt fundamentally similar helical structures in solution, despite distinct CD spectra. The elucidation of detailed structural information for peptoid helices with α-chiral aliphatic side chains will facilitate the mimicry of biomolecules, such as transmembrane protein domains, in a distinctly stable form.",
author = "Wu, {Cindy W.} and Kent Kirshenbaum and Sanborn, {Tracy J.} and Patch, {James A.} and Kai Huang and Dill, {Ken A.} and Zuckermann, {Ronald N.} and Barron, {Annelise E.}",
year = "2003",
month = "11",
day = "5",
doi = "10.1021/ja037540r",
language = "English (US)",
volume = "125",
pages = "13525--13530",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "44",

}

TY - JOUR

T1 - Structural and Spectroscopic Studies of Peptoid Oligomers with α-Chiral Aliphatic Side Chains

AU - Wu, Cindy W.

AU - Kirshenbaum, Kent

AU - Sanborn, Tracy J.

AU - Patch, James A.

AU - Huang, Kai

AU - Dill, Ken A.

AU - Zuckermann, Ronald N.

AU - Barron, Annelise E.

PY - 2003/11/5

Y1 - 2003/11/5

N2 - Substantial progress has been made in the synthesis and characterization of various oligomeric molecules capable of autonomous folding to well-defined, repetitive secondary structures. It is now possible to investigate sequence-structure relationships and the driving forces for folding in these systems. Here, we present detailed analysis by X-ray crystallography, NMR, and circular dichroism (CD) of the helical structures formed by N-substituted glycine (or "peptoid") oligomers with α-chiral, aliphatic side chains. The X-ray crystal structure of a N-(1-cyclohexylethyl)glycine pentamer, the first reported for any peptoid, shows a helix with cis-amide bonds, ∼3 residues per turn, and a pitch of ∼6.7 Å. The backbone dihedral angles of this pentamer are similar to those of a polyproline type I peptide helix, in agreement with prior modeling predictions. This crystal structure likely represents the major solution conformers, since the CD spectra of analogous peptoid hexamers, dodecamers, and pentadecamers, composed entirely of either (S)-N-(1-cyclohexylethyl)glycine or (S)-N-(sec-butyl)glycine monomers, also have features similar to those of the polyproline type I helix. Furthermore, this crystal structure is similar to a solution NMR structure previously described for a peptoid pentamer comprised of chiral, aromatic side chains, which suggests that peptoids containing either aromatic or aliphatic α-chiral side chains adopt fundamentally similar helical structures in solution, despite distinct CD spectra. The elucidation of detailed structural information for peptoid helices with α-chiral aliphatic side chains will facilitate the mimicry of biomolecules, such as transmembrane protein domains, in a distinctly stable form.

AB - Substantial progress has been made in the synthesis and characterization of various oligomeric molecules capable of autonomous folding to well-defined, repetitive secondary structures. It is now possible to investigate sequence-structure relationships and the driving forces for folding in these systems. Here, we present detailed analysis by X-ray crystallography, NMR, and circular dichroism (CD) of the helical structures formed by N-substituted glycine (or "peptoid") oligomers with α-chiral, aliphatic side chains. The X-ray crystal structure of a N-(1-cyclohexylethyl)glycine pentamer, the first reported for any peptoid, shows a helix with cis-amide bonds, ∼3 residues per turn, and a pitch of ∼6.7 Å. The backbone dihedral angles of this pentamer are similar to those of a polyproline type I peptide helix, in agreement with prior modeling predictions. This crystal structure likely represents the major solution conformers, since the CD spectra of analogous peptoid hexamers, dodecamers, and pentadecamers, composed entirely of either (S)-N-(1-cyclohexylethyl)glycine or (S)-N-(sec-butyl)glycine monomers, also have features similar to those of the polyproline type I helix. Furthermore, this crystal structure is similar to a solution NMR structure previously described for a peptoid pentamer comprised of chiral, aromatic side chains, which suggests that peptoids containing either aromatic or aliphatic α-chiral side chains adopt fundamentally similar helical structures in solution, despite distinct CD spectra. The elucidation of detailed structural information for peptoid helices with α-chiral aliphatic side chains will facilitate the mimicry of biomolecules, such as transmembrane protein domains, in a distinctly stable form.

UR - http://www.scopus.com/inward/record.url?scp=0242299241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242299241&partnerID=8YFLogxK

U2 - 10.1021/ja037540r

DO - 10.1021/ja037540r

M3 - Article

VL - 125

SP - 13525

EP - 13530

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 44

ER -