eprintid: 13619
rev_number: 10
userid: 1089
dir: disk0/00/01/36/19
datestamp: 2012-09-28 00:09:59
lastmod: 2017-09-27 05:15:08
status_changed: 2012-09-28 00:09:59
type: thesis_degree
metadata_visibility: show
contact_email: melissaliberatore@gmail.com
item_issues_count: 0
eprint_status: archive
creators_name: Liberatore, Melissa
creators_email: mal84@pitt.edu
creators_id: MAL84
title: SYNTHESIS AND NMR STUDIES OF A β-TURN MIMETIC MOLECULAR    TORSION BALANCE
ispublished: unpub
divisions: sch_as_chemistry
full_text_status: public
keywords: torsion balance, NMR, hydrogen bond, antiparallel beta sheet, conformational dynamics
abstract: The attainment of precise measurements of the molecular forces that influence protein folding is important in order to further understand peptide dynamics and stability. A hybrid synthetic-natural peptide motif, combining an o,o,o’-trisubstituted biphenyl with an (ortho-tolyl)-amide, was synthesized in multiple formats and studied by NMR to probe the effects of amino acid substitutions on antiparallel beta-sheet configuration and stability. The potential of this “molecular torsion balance” as a beta-turn mimic was demonstrated by quantifying the rotational barriers about several axes. The free-energy rotational barrier of the aryl-aryl bond was found to be 35.7 kcal mol-1 at 418 K in hexanes.  EXSY analysis was also used to measure barriers about the N-aryl (20.9 kcal mol-1 at 343 K in toluene-d8) and N-CO bonds (17.2 kcal mol-1 at 298 K in chloroform-d). The N-aryl barriers of a zwitterionic torsion balance containing a single alanine residue (19.7 kcal mol-1 in acetonitrile-d3 at 343 K, and 22.6 kcal mol-1 in deuterated buffer pD 6.9 at 373 K) showed that rotation about this bond is slower in water, most likely due to the propensity of water to form hydrogen bonds with the charged moieties participating in a salt bridge. Torsion balances were used to study intramolecular hydrogen bond preference by analyzing 1H NMR peak data. An amino acid chain (a single alanine or glycine residue) was found to preferably hydrogen bond with an amide versus an ester carbonyl (1.4:1.0 at 298 K in toluene-d8), and with a secondary amide versus a tertiary amide carbonyl (observation of tertiary amide proton coalescence via variable temperature NMR, from 303 K to 343 K, in toluene-d8). The overall findings suggest that this hybrid torsion balance is a valuable tool that can provide data on conformational dynamics and can examine hydrogen bond and salt bridge interactions of an antiparallel beta-sheet scaffold.
date: 2012-09-27
date_type: published
pages: 234
institution: University of Pittsburgh
refereed: TRUE
etdcommittee_type: committee_chair
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_name: Wilcox, Craig
etdcommittee_name: Curran, Dennis
etdcommittee_name: Trakselis, Michael
etdcommittee_name: Klein-Seetharaman, Judith
etdcommittee_email: daylite@pitt.edu
etdcommittee_email: curran@pitt.edu
etdcommittee_email: mtraksel@pitt.edu
etdcommittee_email: jks33@pitt.edu
etdcommittee_id: DAYLITE
etdcommittee_id: CURRAN
etdcommittee_id: MTRAKSEL
etdcommittee_id: JKS33
etd_defense_date: 2012-07-23
etd_approval_date: 2012-09-27
etd_submission_date: 2012-08-16
etd_release_date: 2012-09-27
etd_access_restriction: 5_year
etd_patent_pending: FALSE
thesis_type: dissertation
degree: PhD
citation:   Liberatore, Melissa  (2012) SYNTHESIS AND NMR STUDIES OF A β-TURN MIMETIC MOLECULAR TORSION BALANCE.  Doctoral Dissertation, University of Pittsburgh.    (Unpublished)  
document_url: http://d-scholarship-dev.library.pitt.edu/13619/1/M_Liberatore_PhD_dissertation_final_draft_August_2012.pdf