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 (⌬ acid H) were determined to be 323.9 Ϯ 2.5 kcal/mol (CysGly 3 NH 2 ), 319.2 Ϯ 2.3 kcal/mol (CysGly 4 NH 2 ), 333.8 Ϯ 2.1 kcal/mol (Gly 3 CysNH 2 ), and 321.9 Ϯ 2.8 kcal/mol (Gly 4 CysNH 2 ), respectively. The corresponding deprotonation entropies (⌬ acid S) of the peptides were estimated. The gas-phase acidities (⌬ acid G) were derived to be 318.4 Ϯ 2.5 kcal/mol (CysGly 3 NH 2 ), 314.9 Ϯ 2.3 kcal/mol (CysGly 4 NH 2 ), 327.5 Ϯ 2.1 kcal/mol (Gly 3 CysNH 2 ), and 317.4 Ϯ 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/6-31ϩG(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) Ϫ NH 2 , are also random coils. The two N-cysteine anionic peptides, (Cys-H) Ϫ 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. (J Am Soc Mass Spectrom 2010, 21, 603-614)

Comparison of the pH‐dependent formation of His and Cys heptapeptide complexes of nickel(II), copper(II), and zinc(II) as determined by ion mobility‐mass spectrometry

“…Our previous study of A to F located low energy B3LYP/LanL2DZ conformers of [amb 5 ‐H] − that were stabilized by the Cys thiolate and C‐terminus carboxylate salt‐bridged or H‐bonded to the imidazolium or imidazole groups of His. These conformers were also in agreement with previous studies of the deprotonation of cysteine at the side chain rather than the amidated C‐terminus …”

Matrix-assisted laser desorption/ionisation mass spectrometric response factors of peptides generated using different proteolytic enzymes

“…The effect of the position of the acidic and basic residues on the gas‐phase basicity of small peptides has been reported . Applying the kinetic method, Morishitti et al .…”

“…Applying the kinetic method, Morishitti et al . determined gas‐phase acidities of cysteine–polyglycine peptides, and more acidic behaviour was observed when cysteine is at the N‐terminus than when cysteine is at the C‐terminus . Carr et al .…”

Proton affinity of dipeptides containing alanine and diaminobutyric acid

“…Our previous studies have demonstrated that conformations could significantly influence the gas-phase acidity of oligopeptides. For the series of cysteine (Cys)-containing peptides, the N-Cys peptides were significantly more acidic than the C-Cys peptides [34][35][36]. Computational studies suggested that the deprotonated N-Cys peptides with four residues and longer existed in a helical conformation, while the deprotonated C-Cys peptides preferred a globular conformation [35,36].…”

“…For the series of cysteine (Cys)-containing peptides, the N-Cys peptides were significantly more acidic than the C-Cys peptides [34][35][36]. Computational studies suggested that the deprotonated N-Cys peptides with four residues and longer existed in a helical conformation, while the deprotonated C-Cys peptides preferred a globular conformation [35,36]. The stronger acidity of the N-Cys peptides was mainly due to the favored interaction with the helix macro-dipole that stabilized the N-terminal thiolate anion.…”