Synthesis and mass spectrometry studies of oligopeptides

<p>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.</p><p>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.</p>

Name thesis:degree_name

Master of Science (M.S.)

Level thesis:degree_level

Thesis - Pacific Access Restricted

Discipline thesis:degree_discipline

Pharmaceutical and Chemical Sciences

Year dc:date.available

2012

Author dc:creator

• Sawhney, Ashish

Contributors dc:contributor

• Jianhua Ren

• Amino acids
• Peptides
• Mass spectrometry
• Oligopeptides
• Medicine and Health Sciences

Licence

• http://rightsstatements.org/vocab/InC/1.0/

Repository record dc:identifier

https://scholarlycommons.pacific.edu/uop_etds/831

OAI identifier oai:identifier

oai:scholarlycommons.pacific.edu:uop_etds-1830