Non-classical helix-stabilizing interactions: C-H...O H-bonding between Phe and Glu side chains in alpha-helical peptides.
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 alpha-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.
Shi
Zhengshuang
Z
Department of Chemistry, New York University, New York, NY 10003, USA.
Olson
C Anders
CA
Bell
Anthony J
AJ
Kallenbach
Neville R
NR
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D018698:Glutamic Acid / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry*; D012492:Salts
D010455:Peptides; D012492:Salts; D018698:Glutamic Acid; D010649:Phenylalanine