title: Helicity of short E-R/K peptides.
abstract: Understanding the secondary structure of peptides is important in protein folding, enzyme function, and peptide-based drug design. Previous studies of synthetic Ala-based peptides (>12 a.a.) have demonstrated the role for charged side chain interactions involving Glu/Lys or Glu/Arg spaced three (i, i + 3) or four (i, i + 4) residues apart. The secondary structure of short peptides (<9 a.a.), however, has not been investigated. In this study, the effect of repetitive Glu/Lys or Glu/Arg side chain interactions, giving rise to E-R/K helices, on the helicity of short peptides was examined using circular dichroism. Short E-R/K-based peptides show significant helix content. Peptides containing one or more E-R interactions display greater helicity than those with similar E-K interactions. Significant helicity is achieved in Arg-based E-R/K peptides eight, six, and five amino acids long. In these short peptides, each additional i + 3 and i + 4 salt bridge has substantial contribution to fractional helix content. The E-R/K peptides exhibit a strongly linear melt curve indicative of noncooperative folding. The significant helicity of these short peptides with predictable dependence on number, position, and type of side chain interactions makes them an important consideration in peptide design.
authors.affiliation: Department of Biochemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Sommese
authors.forename: Sivaraj
authors.initials: S
authors.lastname: Sivaramakrishnan
authors.forename: Robert L
authors.initials: RL
authors.lastname: Baldwin
authors.forename: James A
authors.initials: JA
authors.lastname: Spudich
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry*; D002942:Circular Dichroism; D018698:Glutamic Acid / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D009842:Oligopeptides; D018698:Glutamic Acid; D001120:Arginine; D008239:Lysine