Transition state analysis of thymidine phosphorylase from E. coli. Rezaei, Mansoureh en_US
dc.contributor.department Chemistry en_US 2014-06-20T17:39:22Z 2014-06-20T17:39:22Z 2001 en_US
dc.description.abstract Thymidine phosphorylase (E.C. (TP) is an enzyme involved in the reversible conversion of thymidine, deoxyuridine, and their analogs to their respective bases and 2-alpha-D-deoxyribose-1-phosphate. This enzyme is identical to an angiogenic factor, platelet-derived endothelial cell growth factor. TP is expressed at high levels in a wide variety of solid tumors and is known to promote the development of new blood vessels, which are fundamental to tumor growth and metastasis. en_US
dc.description.abstract The transition state of thymidine phosphorylase has been characterized by kinetic isotope effects, bond-energy bond-order vibrational analysis, and molecular electrostatic potential surface and quantum chemical calculations. Kinetic isotope effects for arsenolysis were measured by liquid chromatography/mass spectrometry for [1'-2H], [2' -2H], [5'-2H], [1'-13C], [2' -13C), and [1-15N] uridine to provide experimental values of 1.144 +/- 0.050, 0.959 +/- 0.012, 0.988 +/- 0.127, 1.013 +/- 0.007, 0.995 +/- 0.002, and 1.027 +/- 0.046 respectively. These kinetic isotope effects were matched to a geometric transition state model selected by bond-energy bond-order vibrational analysis (BEBOVIB-IV program). en_US
dc.description.abstract The transition state can be described as an SN1 type reaction with oxocarbenium ion character with slight hyperconjugation existing between the C2'-H2' and C1'-N1 bonds, and C4 '-endo and C3'- exo conformation of furanose ring due to protonation of O2 in the uracil ring. Protonation of O2 also assists departure of the uracil. From the BEBOVIB-IV calculations, the 13C isotope effect predicts a bond order of 0.78 for C1'-N 1, indicating an early transition state. en_US
dc.description.abstract Inhibitor design for thymidine phosphorylase was attempted by incorporating features of the transition state. en_US D.A. en_US
dc.publisher Middle Tennessee State University en_US
dc.subject.lcsh Chemistry, Biochemistry en_US
dc.subject.lcsh Chemistry, Physical en_US
dc.thesis.degreegrantor Middle Tennessee State University en_US
dc.thesis.degreelevel Doctoral en_US
dc.title Transition state analysis of thymidine phosphorylase from E. coli. en_US
dc.type Dissertation en_US
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