title: Effect of side chain length on intrahelical interactions between carboxylate- and guanidinium-containing amino acids.
abstract: 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. Furthermore, the Arg-containing peptides consistently exhibited higher helicity compared to the corresponding Agp-, Agb-, and Agh-containing peptides. Side chain conformational analysis by molecular mechanics calculations showed that the Zbb-Xaa (i, i + 3) and (i, i + 4) interactions mainly involved the χ 1 dihedral combinations (g+, g+) and (g-, g+), respectively. These low energy conformations were also observed in intrahelical Asp-Arg and Glu-Arg salt bridges of natural proteins. Accordingly, Asp and Glu provides variation in helix characteristics associated with Arg, but Aad does not provide features beyond those already delivered by Glu. Importantly, nature may have chosen the side chain length of Arg to support helical conformations through inherent high helix propensity coupled with stabilizing intrahelical ion pairing interactions with the carboxylate-containing residues.
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei, 10617, Taiwan.
authors.forename: Hsiou-Ting
authors.initials: HT
authors.lastname: Kuo
authors.forename: Po-An
authors.initials: PA
authors.lastname: Yang
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Wang
authors.forename: Hao-Chun
authors.initials: HC
authors.lastname: Hsu
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Wu
authors.forename: Yu-Te
authors.initials: YT
authors.lastname: Ting
authors.forename: Ming-Huei
authors.initials: MH
authors.lastname: Weng
authors.forename: Li-Hung
authors.initials: LH
authors.lastname: Kuo
authors.forename: Richard P
authors.initials: RP
authors.lastname: Cheng
mesh_terms: D015074:2-Aminoadipic Acid / Q000737:chemistry; D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D001120:Arginine / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D002942:Circular Dichroism; D018698:Glutamic Acid / Q000737:chemistry; D019791:Guanidine / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D002264:Carboxylic Acids; D010455:Peptides; D015074:2-Aminoadipic Acid; C023997:alpha-amino-beta-guanidinopropionic acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D001120:Arginine; D019791:Guanidine; D000409:Alanine