Campus Access Only

All rights reserved. This publication is intended for use solely by faculty, students, and staff of University of the Pacific. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, now known or later developed, including but not limited to photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author or the publisher.

Date of Award

2016

Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

Jianhua Ren

First Committee Member

Andreas Franz

Second Committee Member

Ryan Moffet

Third Committee Member

Jerry Tsai

Fourth Committee Member

Craig Vierra

Abstract

The data presented in this thesis is a comprehensive study on the nature of peptide structure and how subtle and systematic changes in sequence and sidechain affect the basicity, ion stability, and conformation of a peptide. The peptides characterized were acetylated polyalanine di-, tri-, and tetra- peptides containing a proton-accepting probe: lysine and or the non-proteinogenic lysine-homologs: ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid. Peptides were studied in isomeric pairs for which the basic amino acid was placed closest to the N-terminus or the C-terminus of each peptide family (A n Probe vs. ProbeA n ). Using a variety of mass spectrometry based techniques and infrared multiphoton dissociation ion spectroscopy, the isomeric families of polyalanine peptides were characterized. Quantum chemical techniques were employed in parallel to provide theoretical predictions of three-dimensional structure, physical properties (dipole moment, polarizability, and accessible surface area), thermochemical values, and vibrational IR spectra, to gain further understanding of the peptides studied and to push the limits of current theoretical models. Overall it was found that the AnProbe peptide was more basic than their ProbeAn isomer. For the dipeptide systems, the greater basicity of AProbe peptides was due to efficiently charge-solvated ions which formed more compact structures compared to their ProbeA counterpart. For the tri- and tetra- peptide systems, greater basicity of the A 2,3 Probe peptides was likely due to formation of α or 3 10 helix-like structures in the protonated forms., introducing the macrodipolar effect, which cooperatively encouraged helical formation while stabilizing the charged site. On the other hand, ProbeA 2,3 peptides formed charge-solvated coils which do not exhibit any kind of dipole effect, resulting in lower basicity than their A2,3Probe counterpart.

Pages

252

ISBN

9781369117271

To access this thesis/dissertation you must have a valid pacific.edu email address and create an account for Scholarly Commons.

Find in ProQuest

Share

COinS

If you are the author and would like to grant permission to make your work openly accessible, please email