Experimental and Computational Studies in Bioorganic and Synthetic Organic Chemistry

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dc.contributor.authorLam, Polo Chun Hungen
dc.contributor.committeechairCarlier, Paul R.en
dc.contributor.committeememberTanko, James M.en
dc.contributor.committeememberGandour, Richard D.en
dc.contributor.committeememberDeck, Paul A.en
dc.contributor.committeememberKingston, David G. I.en
dc.contributor.departmentChemistryen
dc.date.accessioned2014-03-14T21:21:40Zen
dc.date.adate2004-12-13en
dc.date.available2014-03-14T21:21:40Zen
dc.date.issued2004-10-12en
dc.date.rdate2004-12-13en
dc.date.sdate2004-10-20en
dc.description.abstractCationâ Ï interaction is an important determinant in protein structure and function. Among the three proteinogenic aromatic amino acids, tryptophan (Trp) is the strongest cationâ Ï donor. We reported the asymmetric syntheses of tryptophan regioisomers in which the amino acid side chain is attached at different position of the indole moiety. These new tryptophan regioisomers can effect a different mode of cationâ Ï interaction. In nature, dramatic increases in binding affinity can be achieved through multivalent binding. Following a fragmentation-dimerization approach, we synthesized Taxol-based dimer in which the baccatin III core of Taxol is coupled with flexible PEG linker. However, microtubule assembly assay suggested that these new dimers are not capable of effecting bivalent binding to the Taxol binding sites in microtubules. Memory of chirality (MOC) is an emerging theme in asymmetric synthesis in which the dynamic chirality of the reactive intermediate "memorizes" the static chirality of the reactant. Using dynamic 1D and 2D NMR and density functional theory (DFT) methods, we studied the MOC effect of 1,4-benzodiazepin-2-ones. Reconstruction of the reaction pathway using DFT calculations supported our proposed contra steric, retention of configuration mechanism.en
dc.description.degreePh. D.en
dc.identifier.otheretd-10202004-130155en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-10202004-130155/en
dc.identifier.urihttp://hdl.handle.net/10919/40013en
dc.publisherVirginia Techen
dc.relation.haspartVita.pdfen
dc.relation.haspartAbstract.pdfen
dc.relation.haspartThesis.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectMemory of Chiralityen
dc.subjectMicrotubulesen
dc.subjectDynamic Chiralityen
dc.subjectDensity Functional Theoryen
dc.subjectDynamic NMRen
dc.subjectCation-Pi Interactionen
dc.subjectAmino Acidsen
dc.subjectAsymmetric Synthesisen
dc.subjectPEGen
dc.subjectTaxolen
dc.subjectPaclitaxelen
dc.subjectMultivalent Bindingen
dc.subjectTryptophanen
dc.titleExperimental and Computational Studies in Bioorganic and Synthetic Organic Chemistryen
dc.typeDissertationen
thesis.degree.disciplineChemistryen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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