title: Gas-phase acidities of cysteine-polyglycine peptides: the effect of the cysteine position.
abstract: The sequence and conformational effects on the gas-phase acidities of peptides have been studied by using two pairs of isomeric cysteine-polyglycine peptides, CysGly(3,4)NH(2) and Gly(3,4)CysNH(2). The extended Cooks kinetic method was employed to determine the gas-phase acidities using a triple quadrupole mass spectrometer with an electrospray ionization source. The ion activation was achieved via collision-induced dissociation experiments. The deprotonation enthalpies (Delta(acid)H) were determined to be 323.9 +/- 2.5 kcal/mol (CysGly(3)NH(2)), 319.2 +/- 2.3 kcal/mol (CysGly(4)NH(2)), 333.8 +/- 2.1 kcal/mol (Gly(3)CysNH(2)), and 321.9 +/- 2.8 kcal/mol (Gly(4)CysNH(2)), respectively. The corresponding deprotonation entropies (Delta(acid)S) of the peptides were estimated. The gas-phase acidities (Delta(acid)G) were derived to be 318.4 +/- 2.5 kcal/mol (CysGly(3)NH(2)), 314.9 +/- 2.3 kcal/mol (CysGly(4)NH(2)), 327.5 +/- 2.1 kcal/mol (Gly(3)CysNH(2)), and 317.4 +/- 2.8 kcal/mol (Gly(4)CysNH(2)), respectively. Conformations and energetic information of the neutral and anionic peptides were calculated through simulated annealing (Tripos), geometry optimization (AM1), and single point energy calculations (B3LYP/6-31+G(d)), respectively. Both neutral and deprotonated peptides adopt many possible conformations of similar energies. All neutral peptides are mainly random coils. The two C-cysteine anionic peptides, Gly(3,4)(Cys-H)(-)NH(2), are also random coils. The two N-cysteine anionic peptides, (Cys-H)(-)Gly(3,4)NH(2), may exist in both random coils and stretched helices. The two N-cysteine peptides, CysGly(3)NH(2) and CysGly(4)NH(2), are significantly more acidic than the corresponding C-terminal cysteine ones, Gly(3)CysNH(2) and Gly(4)CysNH(2). The stronger acidities of the former may come from the greater stability of the thiolate anion resulting from the interaction with the helix-macrodipole, in addition to the hydrogen bonding interactions.
authors.affiliation: Department of Chemistry, University of the Pacific, Stockton, California 95211, USA.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Morishetti
authors.forename: Betty De Suan
authors.initials: Bde S
authors.lastname: Huang
authors.forename: Jessica Marney
authors.initials: JM
authors.lastname: Yates
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ren
mesh_terms: D000595:Amino Acid Sequence; D003545:Cysteine / Q000737:chemistry*; D005740:Gases / Q000737:chemistry*; D007536:Isomerism; D008969:Molecular Sequence Data; D010449:Peptide Mapping / Q000379:methods*; D010455:Peptides / Q000737:chemistry*; D044367:Phase Transition; D011487:Protein Conformation
chemical_list: D005740:Gases; D010455:Peptides; C011080:polyglycine; D003545:Cysteine