Gas-Phase Acidities of the Cysteine-Polyalanine Peptides I: A_3,4CSH and HSCA_3,4

Authors

Jianhua Ren, University of the PacificFollow
John P. Tan, University of California, Los Angeles
Robert T. Harper, Lincoln High School

Document Type

Article

Publication Title

Journal of Physical Chemistry A

Department

Chemistry

ISSN

1089-5639

Volume

113

Issue

41

DOI

10.1021/jp903594a

First Page

10903

Last Page

10912

Publication Date

9-15-2009

Abstract

The gas-phase acidities of four cysteine-polyalanine peptides, A_3,4CSH and HSCA_3,4, were determined using the extended Cooks kinetic method with full entropy analysis. A triple-quadrupole mass spectrometer with an electrospray interface was employed for the experimental study. The ion activation was achieved via collision-induced dissociation (CID) experiments. The deprotonation enthalpies (Δ_acidH) of the peptides were determined to be 332.2 ± 2.0 kcal/mol (A₃CSH), 325.9 ± 2.0 kcal/mol (A₄CSH), 319.3 ± 3.0 kcal/mol (HSCA₃), and 319.2 ± 4.0 kcal/mol (HSCA₄). The deprotonation entropies (Δ_acidS) of the peptides were estimated based on the entropy term (Δ(ΔS)) and the deprotonation entropies of the reference acids. By using the deprotonation enthalpies and entropies, the gas-phase acidities (Δ_acidG) of the peptides were derived: 325.0 ± 2.0 kcal/mol (A₃CSH), 320.2 ± 2.0 kcal/mol (A₄CSH), 316.3 ± 3.0 kcal/mol (HSCA₃), and 315.4 ± 4.0 kcal/mol (HSCA₄). Conformations and energetic information of the peptides were calculated through simulated annealing (Tripos), geometry optimization (AM1), and single-point energy calculations (B3LYP/6-31+G(d)), respectively. The calculated theoretical deprotonation enthalpies (Δ_acidH) of 334.2 kcal/mol (A₃CSH), 327.7 kcal/mol (A₄CSH), 320.6 kcal/mol (HSCA₃), and 318.6 kcal/mol (HSCA₄) are in good agreement with the experimentally determined values. Both the experimental and computational studies suggest that the two N-terminal cysteine peptides, HSCA_3,4, are significantly more acidic than the corresponding C-terminal ones, A_3,4CSH. The high acidities of the former are likely due to the helical conformational effects for which the thiolate anion may be strongly stabilized by the interaction with the helix macrodipole.

Recommended Citation

Ren, J., Tan, J. P., & Harper, R. T. (2009). Gas-Phase Acidities of the Cysteine-Polyalanine Peptides I: A_3,4CSH and HSCA_3,4. Journal of Physical Chemistry A, 113(41), 10903–10912. DOI: 10.1021/jp903594a
https://scholarlycommons.pacific.edu/cop-facarticles/667