Gas-Phase Acidities of Cysteine-Polyglycine Peptides: The Effect of the Cysteine Position

Authors

Kiran Kumar Morishetti, University of the Pacific
Betty De Suan Huang, University of the Pacific
Jessica Marney Yates, University of the Pacific
Jianhua Ren, University of the PacificFollow

Document Type

Article

Publication Title

Journal of the American Society for Mass Spectrometry

Department

Chemistry

ISSN

1044-0305

Volume

21

Issue

4

DOI

10.1016/j.jasms.2009.12.008

First Page

603

Last Page

614

Publication Date

4-1-2010

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_3,4NH₂ and Gly_3,4CysNH₂. 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 (Δ_acidH) were determined to be 323.9 ± 2.5 kcal/mol (CysGly₃NH₂), 319.2 ± 2.3 kcal/mol (CysGly₄NH₂), 333.8 ± 2.1 kcal/mol (Gly₃CysNH₂), and 321.9 ± 2.8 kcal/mol (Gly₄CysNH₂), respectively. The corresponding deprotonation entropies (Δ_acidS) of the peptides were estimated. The gas-phase acidities (Δ_acidG) were derived to be 318.4 ± 2.5 kcal/mol (CysGly₃NH2), 314.9 ± 2.3 kcal/mol (CysGly₄NH2), 327.5 ± 2.1 kcal/mol (Gly₃CysNH₂), and 317.4 ± 2.8 kcal/mol (Gly₄CysNH₂), 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)⁻NH₂, are also random coils. The two N-cysteine anionic peptides, (Cys-H)⁻Gly_3,4NH₂, may exist in both random coils and stretched helices. The two N-cysteine peptides, CysGly₃NH₂ and CysGly₄NH₂, are significantly more acidic than the corresponding C-terminal cysteine ones, Gly₃CysNH₂ and Gly₄CysNH₂. 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.

Recommended Citation

Morishetti, K. K., Huang, B. D., Yates, J. M., & Ren, J. (2010). Gas-Phase Acidities of Cysteine-Polyglycine Peptides: The Effect of the Cysteine Position. Journal of the American Society for Mass Spectrometry, 21(4), 603–614. DOI: 10.1016/j.jasms.2009.12.008
https://scholarlycommons.pacific.edu/cop-facarticles/680