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dc.contributor.advisorGates, Kent S. (Kent Stephen), 1962-eng
dc.contributor.authorGamboa Varela, Jacquelineeng
dc.date.issued2017eng
dc.date.submitted2017 Springeng
dc.descriptionField of study: Chemistry.eng
dc.descriptionProf. Kent S. Gates, PhD--Dissertation Supervisor.eng
dc.descriptionIncludes vita.eng
dc.description"May 2017."eng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] DNA is the central molecule of biology as it stores the genetic information for cells to properly function and develop. Modifications to the DNA can stall cellular processes such as replication and transcription, leading the cell to recruit repair machinery or in some cases undergo apoptosis. Interstrand cross-links are particularly significant types of DNA damage because they prevent strand separation required for replication and transcription. Cross-links involve bonding between the two strands of DNA. The rate and mechanism of cross-link repair in cells are not well understood. A significant challenge in the study of cross-link repair is the synthesis of chemically well-defined DNA cross-links. Here we summarize the preparation of cross-links derived from the hydrazone formation between a non-natural nucleobase N4-aminocytidine and abasic sites in duplex DNA. The cross-link was generated rapidly and in high yield. The cross-link is stable under physiological conditions but, interestingly, can be reversibly dissociated and re-formed by thermal cycling between 20-80 [degrees]C. We provided evidence that the cross-link is stable against multiple agents and the cross-link is reversible. We used this chemistry to prepare structurally diverse cross-links for the utilization in cross-link repair studies. Overall, we developed a synthetic cross-link that is easily and rapidly prepared from commercially available reagents in high yields, at defined locations in duplexed DNA.eng
dc.description.bibrefIncludes bibliographical references.eng
dc.format.extent1 online resource (xvi, 148 pages) : illustrations (some color)eng
dc.identifier.merlinb12919766xeng
dc.identifier.oclc1099255214eng
dc.identifier.urihttps://hdl.handle.net/10355/63397
dc.identifier.urihttps://doi.org/10-32469/10355/63397eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess to files is limited to the University of Missouri--Columbia.eng
dc.titleFast, inexpensive, high-yielding, site-selective, chemical synthesis of cross-linked DNA duplexes via hydrazone formation between N[superscript 4]-aminocytidine and Ap-siteseng
dc.typeThesiseng
thesis.degree.disciplineChemistry (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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