?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F13619%2F&rft.title=SYNTHESIS+AND+NMR+STUDIES+OF+A+%CE%B2-TURN+MIMETIC+MOLECULAR++++TORSION+BALANCE&rft.creator=Liberatore%2C+Melissa&rft.description=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%2C+combining+an+o%2Co%2Co%E2%80%99-trisubstituted+biphenyl+with+an+(ortho-tolyl)-amide%2C+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+%E2%80%9Cmolecular+torsion+balance%E2%80%9D+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%2C+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%2C+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%3A1.0+at+298+K+in+toluene-d8)%2C+and+with+a+secondary+amide+versus+a+tertiary+amide+carbonyl+(observation+of+tertiary+amide+proton+coalescence+via+variable+temperature+NMR%2C+from+303+K+to+343+K%2C+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.&rft.date=2012-09-27&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F13619%2F1%2FM_Liberatore_PhD_dissertation_final_draft_August_2012.pdf&rft.identifier=++Liberatore%2C+Melissa++(2012)+SYNTHESIS+AND+NMR+STUDIES+OF+A+%CE%B2-TURN+MIMETIC+MOLECULAR+TORSION+BALANCE.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++