Cation-π interaction in model α-helical peptides

Zhengshuang Shi, C. Anders Olson, Neville R. Kallenbach

Research output: Contribution to journalArticle

Abstract

Cation-π interactions are increasingly recognized as important in chemistry and biology. Here we investigate the cation--π interaction by determining its effect on the helicity of model peptides using a combination of CD and NMR spectroscopy. The data show that a single Trp/Arg interaction on the surface of a peptide can make a significant net favorable free energy contribution to helix stability if the two residues are positioned with appropriate spacing and orientation. The solvent-exposed Trp→Arg (i, i + 4) interaction in helices can contribute -0.4 kcal/mol to the helix stability, while no free energy gain is detected if the two residues have the reversed orientation, Arg→Trp (i, i + 4). The derived free energy is consistent with other experimental results studied in proteins or model peptides on cation-π interactions. However in the same system the postulated Phe/Arg (i, i + 4) cation-π interaction provides no net free energy to helix stability. Thus the Trp→Arg interaction is stronger than Phe→Arg. The cation-π interactions are not sensitive to the screening effect by adding neutral salt as indicated by salt titration. Our results are in qualitative agreement with theoretical calculations emphasizing that cation-π interactions can contribute significantly to protein stability with the order Trp > Phe. However, our and other experimental values are significantly smaller than estimates from theoretical calculations.

Original languageEnglish (US)
Pages (from-to)3284-3291
Number of pages8
JournalJournal of the American Chemical Society
Volume124
Issue number13
DOIs
StatePublished - Apr 3 2002

Fingerprint

Peptides
Cations
Positive ions
Free energy
Salts
Proteins
Protein Stability
Titration
Nuclear magnetic resonance spectroscopy
Screening
Magnetic Resonance Spectroscopy

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Cation-π interaction in model α-helical peptides. / Shi, Zhengshuang; Olson, C. Anders; Kallenbach, Neville R.

In: Journal of the American Chemical Society, Vol. 124, No. 13, 03.04.2002, p. 3284-3291.

Research output: Contribution to journalArticle

Shi, Zhengshuang ; Olson, C. Anders ; Kallenbach, Neville R. / Cation-π interaction in model α-helical peptides. In: Journal of the American Chemical Society. 2002 ; Vol. 124, No. 13. pp. 3284-3291.
@article{1cd4221188ca43f1b775912f941c137b,
title = "Cation-π interaction in model α-helical peptides",
abstract = "Cation-π interactions are increasingly recognized as important in chemistry and biology. Here we investigate the cation--π interaction by determining its effect on the helicity of model peptides using a combination of CD and NMR spectroscopy. The data show that a single Trp/Arg interaction on the surface of a peptide can make a significant net favorable free energy contribution to helix stability if the two residues are positioned with appropriate spacing and orientation. The solvent-exposed Trp→Arg (i, i + 4) interaction in helices can contribute -0.4 kcal/mol to the helix stability, while no free energy gain is detected if the two residues have the reversed orientation, Arg→Trp (i, i + 4). The derived free energy is consistent with other experimental results studied in proteins or model peptides on cation-π interactions. However in the same system the postulated Phe/Arg (i, i + 4) cation-π interaction provides no net free energy to helix stability. Thus the Trp→Arg interaction is stronger than Phe→Arg. The cation-π interactions are not sensitive to the screening effect by adding neutral salt as indicated by salt titration. Our results are in qualitative agreement with theoretical calculations emphasizing that cation-π interactions can contribute significantly to protein stability with the order Trp > Phe. However, our and other experimental values are significantly smaller than estimates from theoretical calculations.",
author = "Zhengshuang Shi and Olson, {C. Anders} and Kallenbach, {Neville R.}",
year = "2002",
month = "4",
day = "3",
doi = "10.1021/ja0174938",
language = "English (US)",
volume = "124",
pages = "3284--3291",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "13",

}

TY - JOUR

T1 - Cation-π interaction in model α-helical peptides

AU - Shi, Zhengshuang

AU - Olson, C. Anders

AU - Kallenbach, Neville R.

PY - 2002/4/3

Y1 - 2002/4/3

N2 - Cation-π interactions are increasingly recognized as important in chemistry and biology. Here we investigate the cation--π interaction by determining its effect on the helicity of model peptides using a combination of CD and NMR spectroscopy. The data show that a single Trp/Arg interaction on the surface of a peptide can make a significant net favorable free energy contribution to helix stability if the two residues are positioned with appropriate spacing and orientation. The solvent-exposed Trp→Arg (i, i + 4) interaction in helices can contribute -0.4 kcal/mol to the helix stability, while no free energy gain is detected if the two residues have the reversed orientation, Arg→Trp (i, i + 4). The derived free energy is consistent with other experimental results studied in proteins or model peptides on cation-π interactions. However in the same system the postulated Phe/Arg (i, i + 4) cation-π interaction provides no net free energy to helix stability. Thus the Trp→Arg interaction is stronger than Phe→Arg. The cation-π interactions are not sensitive to the screening effect by adding neutral salt as indicated by salt titration. Our results are in qualitative agreement with theoretical calculations emphasizing that cation-π interactions can contribute significantly to protein stability with the order Trp > Phe. However, our and other experimental values are significantly smaller than estimates from theoretical calculations.

AB - Cation-π interactions are increasingly recognized as important in chemistry and biology. Here we investigate the cation--π interaction by determining its effect on the helicity of model peptides using a combination of CD and NMR spectroscopy. The data show that a single Trp/Arg interaction on the surface of a peptide can make a significant net favorable free energy contribution to helix stability if the two residues are positioned with appropriate spacing and orientation. The solvent-exposed Trp→Arg (i, i + 4) interaction in helices can contribute -0.4 kcal/mol to the helix stability, while no free energy gain is detected if the two residues have the reversed orientation, Arg→Trp (i, i + 4). The derived free energy is consistent with other experimental results studied in proteins or model peptides on cation-π interactions. However in the same system the postulated Phe/Arg (i, i + 4) cation-π interaction provides no net free energy to helix stability. Thus the Trp→Arg interaction is stronger than Phe→Arg. The cation-π interactions are not sensitive to the screening effect by adding neutral salt as indicated by salt titration. Our results are in qualitative agreement with theoretical calculations emphasizing that cation-π interactions can contribute significantly to protein stability with the order Trp > Phe. However, our and other experimental values are significantly smaller than estimates from theoretical calculations.

UR - http://www.scopus.com/inward/record.url?scp=0037012361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037012361&partnerID=8YFLogxK

U2 - 10.1021/ja0174938

DO - 10.1021/ja0174938

M3 - Article

VL - 124

SP - 3284

EP - 3291

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 13

ER -