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Synthesis and mass spectrometry studies of oligopeptides

Author

Ashish Sawhney, University of the Pacific

Date of Award

2012

Document Type

Thesis - Pacific Access Restricted

Degree Name

Master of Science (M.S.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

Jianhua Ren

First Committee Member

Liang Xue

Second Committee Member

Ryan Moffet

Third Committee Member

William Stringfellow

Abstract

This thesis discusses two major projects. The first project focuses on understanding the effect of chirality on intrinsic acidity of oligopeptides. Gas-phase acidity (Δ_acidG) and related thermochemical parameters (Δ_acidH, and Δ_acidS), of model N- and C-terminal cysteine polyalanine peptides in which one L-alanine was substituted by a D-alanine viz. CAA^DA and AA^DAC, were measured by the extended Cooks kinetic method. Gas-phase acidities of CAA^DA and AA^DAC were measured to be about 318 kcal/mol and 322 kcal/mol, respectively. These values are different from the gas-phase acidities of the all L-amino acid containing analogues of the above peptides, but suggest that D-alanine containing peptides show the same trend as their all L-amino acid analogues with the N-terminal cysteine peptide being more acidic than the C-terminal cysteine peptide. However, the difference in the acidities of CAA^DA and AA^DAC is about 4 kcal/mol which is about half of the difference between their all L-amino acid analogues. These results also suggest that, presumably, a single L-alanine to D-alanine substitution has a moderate effect on the conformation of the respective peptides.

The aim of the second project is to understand how acidic amino acids influence peptide fragmentation during tandem mass spectrometric analysis. A series of model N- and C- terminal glutamic acid polyalanine and polyglycine (EA_n, A_nE (n=2,3); EG_n (n=2,3), G_nE (n=2-4)) and cysteine polyalanine (CA_n, A_nC (n=4-6)) peptides were studied. Primarily, EA_n and EG_n peptides formed b_n ions. In contrast, while EO_n peptides formed all y_n ions, EA_n peptides formed fewer y_n ions. Similarly, A_nE and G_nE peptides also formed b_n ions. No major differences were observed in y_n ion formation. For both sets of peptides, water loss seemed to trend with the position of glutamic acid. CA_n and A_nC peptides also formed b_n ions, just like their glutamic acid counterparts. However, y_n ions were observed only for A_nC peptides. For all sets of peptides, ions related to b_n and y_n ions were also observed.

Pages

163

Recommended Citation

Sawhney, Ashish. (2012). Synthesis and mass spectrometry studies of oligopeptides. University of the Pacific, Thesis - Pacific Access Restricted. https://scholarlycommons.pacific.edu/uop_etds/831