Effect of side chain length on intrahelical interactions between carboxylate- and guanidinium-containing amino acids.

The charge-containing hydrophilic functionalities of encoded charged amino acids are linked to the backbone via different numbers of hydrophobic methylenes, despite the apparent electrostatic nature of protein ion pairing interactions. To investigate the effect of side chain length of guanidinium- and carboxylate-containing residues on ion pairing interactions, α-helical peptides containing Zbb-Xaa (i, i + 3), (i, i + 4) and (i, i + 5) (Zbb = carboxylate-containing residues Aad, Glu, Asp in decreasing length; Xaa = guanidinium residues Agh, Arg, Agb, Agp in decreasing length) sequence patterns were studied by circular dichroism spectroscopy (CD). The helicity of Aad- and Glu-containing peptides was similar and mostly pH independent, whereas the helicity of Asp-containing peptides was mostly pH dependent.

Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate-containing residues and lysine analogues in a β-hairpin.

β-Sheets are one of the fundamental three-dimensional building blocks for protein structures. Oppositely charged amino acids are frequently observed directly across one another in antiparallel sheet structures, suggesting the importance of cross-strand ion pairing interactions. Despite the apparent electrostatic nature of ion pairing interactions, the charged amino acids Asp, Glu, Arg, Lys have different numbers of hydrophobic methylenes linking the charged functionality to the backbone.

Effect of charged amino acid side chain length at non-hydrogen bonded strand positions on β-hairpin stability.

β-Sheets have been implicated in various neurological disorders, and ∼20% of protein residues adopt a sheet conformation. Therefore, studies on the structural origin of sheet stability can provide fundamental knowledge with potential biomedical applications. Oppositely charged amino acids are frequently observed across one another in antiparallel β-sheets.