Gas Phase Acidity of a Cysteine Residue in Small Oligopeptides

Authors

Jialin Shen, University of the Pacific
Jianhua Ren, University of the PacificFollow

Document Type

Article

Publication Title

International Journal of Mass Spectrometry

Department

Chemistry

ISSN

1387-3806

Volume

316--319

DOI

10.1016/j.ijms.2012.01.001

First Page

147

Last Page

156

Publication Date

4-1-2012

Abstract

The conformational effects on the gas-phase acidities of small cysteine-containing peptides were examined using ten oligopeptides. The gas-phase deprotonation enthalpies were measured using the extended Cooks kinetic method with full entropy analysis. The experiments were carried out using a triple quadrupole mass spectrometer. The values of Δ_acidH were determined to be 335.6 ± 1.7 kcal/mol (AlaCysNH₂), 334.6 ± 1.8 kcal/mol (Ala₂CysNH₂), 331.2 ± 1.8 kcal/mol (CysAlaNH₂), 330.5 ± 2.0 kcal/mol (CysAla₂NH₂), 329.7 ± 1.8 kcal/mol (AlaCysAlaNH₂), 335.3 ± 1.8 kcal/mol (GlyCysNH₂), 334.6 ± 1.7 kcal/mol (Gly₂CysNH₂), 330.4 ± 1.8 kcal/mol (CysGlyNH₂), 329.7 ± 1.8 kcal/mol (CysGly₂NH₂), and 327.3 ± 2.0 kcal/mol (GlyCysGlyNH₂). The gas-phase acidities (Δ_acidG) and the deprotonation entropies (Δ_acidS) for these peptides were determined accordingly. These results suggested that the tripeptides were more acidic than the corresponding dipeptides by about 1 kcal/mol, and the N-cysteine peptides were more acidity than the isomeric C-cysteine peptides by about 4 kcal/mol. The initial conformations of the peptides were modeled via a conformational search using the MMFF method. The final geometries and energies were calculated at the B3LYP/6-31++G(d,p) level of theory. The calculated enthalpies of deprotonation agreed reasonably well with the experimental results. The conformations of the deprotonated N-cysteine peptides were more compact than those of the C-cysteine analogues. The more compact conformations allowed more efficient multiple hydrogen-bonding interactions between the thiolate anion and the nearby NH bonds. The greater acidities of the N-cysteine peptides were likely the results of the more favorable hydrogen-bonding and charge–amide dipole interactions that stabilized the thiolate anions more efficiently.

Recommended Citation

Shen, J., & Ren, J. (2012). Gas Phase Acidity of a Cysteine Residue in Small Oligopeptides. International Journal of Mass Spectrometry, 316--319, 147–156. DOI: 10.1016/j.ijms.2012.01.001
https://scholarlycommons.pacific.edu/cop-facarticles/663