The influence of an amino acid on the stability of α-helical structure depends on the position of the residue in the helix with respect to the ends. Short α helices in proteins are stabilized both by H-bonding of the main-chain NH and CO groups and by capping interactions between side chains and unfulfilled peptide groups at the N and C termini. Peptide models based on consensus position-dependent helix sequences allow one to model capping effects in isolated helices and to establish a base line for these interactions in proteins. We report here an extended series of substitutions in the cap positions of our peptide models and the solution structure of peptide S3, with serine at the N-cap position defined as the N-terminal residue with partly helix and partly coil conformation. The resulting model, determined by 2D 1H NMR, is consistent with a structure at the N-cap involving H-bonding between the serine y oxygen and the peptide NH of the glutamic acid residue three amino acids toward the C terminus. A bifurcated H-bond of Ser Oγ with the NH of Asp5 is possible also, since this group is within interacting distance. This provides direct evidence that specific side-chain interactions with the main chain stabilize isolated a-helical structure.
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