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dc.rights.licenseRestricted to current Rensselaer faculty, staff and students. Access inquiries may be directed to the Rensselaer Libraries.
dc.contributorMcGown, Linda Baine
dc.contributorLakshmi, K. V.
dc.contributorLinhardt, Robert J.
dc.contributorSawyer, Shayla Maya Louise
dc.contributor.authorAlbanese, Christina M.
dc.date.accessioned2021-11-03T08:38:17Z
dc.date.available2021-11-03T08:38:17Z
dc.date.created2016-09-27T14:05:24Z
dc.date.issued2016-08
dc.identifier.urihttps://hdl.handle.net/20.500.13015/1732
dc.descriptionAugust 2016
dc.descriptionSchool of Science
dc.description.abstractThe unrelenting demand for affinity reagents in areas such as proteomics, medical diagnostics, and therapeutic treatment has necessitated their further study and development. In recent years, aptamers—short, single-stranded oligonucleotides that bind target molecules with high affinity and specificity—have become increasingly attractive candidates. Since the introduction of the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process in 1990, numerous aptamers have been identified. Despite extensive efforts towards identification of aptamers to new targets, progress has been hindered by the limitations of the SELEX method. Therefore, finding other avenues for aptamer discovery is crucial for further advancement of this field.
dc.description.abstractThe second focus of this dissertation explores the selectivity and diagnostic potential of the G-quadruplex-forming VEGF aptamer. This aptamer selectively binds the VEGF protein, which is present at high serum levels in numerous cancers and diseases. Using an affinity MALDI MS platform, we covalently attached the VEGF aptamer to fused silica MALDI probe surfaces to selectively capture the VEGF protein from a complex mixture of human serum proteins. These results demonstrate the value of our affinity MALDI method and may allow for rapid protein screening of diseases characterized by high VEGF serum levels.
dc.description.abstractTogether, these studies demonstrate the potential of G-quadruplex-forming oligonucleotides, both for use as aptamers and as possible gene regulatory elements in cancer and other diseases.
dc.description.abstractPrevious success in our group with the ERBB2 breast cancer promoter region encouraged expansion of our studies to include other G-rich promoter regions, which is the topic of this dissertation. These studies focus on the G-quadruplex-forming sequences from the c-myc, Rb, and VEGF oncogene promoter regions and their interactions with nuclear and cellular proteins from breast cancer cell lines. We were able to identify several proteins that bind in vitro to the G-quadruplex structures formed by these sequences, which will lead to new aptamers to these protein targets. Studies of these binding interactions in live cells through chromatin immunoprecipitation (ChIP) also indicate that these interactions occur in the chromatin of live cells. Since these oncogenes are overexpressed in many cancers, such binding could play a role in unearthing new cancer biomarkers or drug therapies.
dc.description.abstractThis dissertation first investigates a novel, genome-inspired reverse-selection pathway towards aptamer discovery that was previously introduced in our laboratory. In this approach, genome-inspired DNA sequences are selected as potential aptamers that may specifically bind proteins extracted from human cells. Selectively captured proteins are identified and the DNA-protein binding interactions are analyzed in live cells to determine if the interaction may have biological as well as analytical significance.
dc.language.isoENG
dc.publisherRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofRensselaer Theses and Dissertations Online Collection
dc.subjectChemistry
dc.titleInvestigations of the aptamer capability of g-quadruplex-forming oligonucleotides
dc.typeElectronic thesis
dc.typeThesis
dc.digitool.pid177421
dc.digitool.pid177422
dc.digitool.pid177423
dc.rights.holderThis electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
dc.description.degreePhD
dc.relation.departmentDept. of Chemistry and Chemical Biology


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