Non-classical helix-stabilizing interactions: C-H⋯O H-bonding between Phe and Glu side chains in α-helical peptides

Zhengshuang Shi, C. Anders Olson, Anthony J. Bell, Neville R. Kallenbach

Research output: Contribution to journalArticle

Abstract

The classical picture of H-bonds has evolved considerably. In contrast to earlier expectations, C-H⋯O H-bonds are now known to be prevalent in both small organic and large biological systems. However, there are few reports on the energetic contribution of C-H⋯O H-bonds in protein or polypeptide systems and we do not know whether such interactions are stabilizing. Here we investigate C-H⋯O H-bonding interactions between Phe and Glu side chains by determining their effects on the helicity of model α-helical peptides using a combination of CD and NMR spectroscopy. The results suggest that Glu/Phe C-H⋯O H-bonding interactions stabilize helical structure, but only in the orientation Glu→Phe (N→C). Each Glu→Phe (N→C) interaction can contribute approximately -0.5 kcal mol-1 to the stability of helical peptide. In the reverse orientation, Phe→Glu (N→C) appears to contribute negligibly. pH titrations provide further evidence for the existence of C-H⋯O H-bonds. The C-H⋯O H-bonding interactions in these peptides are insensitive to the screening effect of added neutral salt. Our results provide quantitative energetic information on C-H⋯O H-bonds that should be useful for empirical force-field calibration.

Original languageEnglish (US)
Pages (from-to)267-279
Number of pages13
JournalBiophysical Chemistry
Volume101-102
DOIs
StatePublished - Dec 10 2002

Fingerprint

helices
peptides
Peptides
interactions
Biological systems
Titration
Calibration
Nuclear magnetic resonance spectroscopy
polypeptides
Screening
Magnetic Resonance Spectroscopy
Salts
titration
field theory (physics)
screening
salts
proteins
nuclear magnetic resonance
Proteins
spectroscopy

Keywords

  • α-Helix
  • C-H⋯O H-bonds
  • Energetics
  • Free energy

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Physical and Theoretical Chemistry

Cite this

Non-classical helix-stabilizing interactions : C-H⋯O H-bonding between Phe and Glu side chains in α-helical peptides. / Shi, Zhengshuang; Olson, C. Anders; Bell, Anthony J.; Kallenbach, Neville R.

In: Biophysical Chemistry, Vol. 101-102, 10.12.2002, p. 267-279.

Research output: Contribution to journalArticle

Shi, Zhengshuang ; Olson, C. Anders ; Bell, Anthony J. ; Kallenbach, Neville R. / Non-classical helix-stabilizing interactions : C-H⋯O H-bonding between Phe and Glu side chains in α-helical peptides. In: Biophysical Chemistry. 2002 ; Vol. 101-102. pp. 267-279.
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