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Full-Text Articles in Nucleic Acids, Nucleotides, and Nucleosides

Computational Analysis Of O6-Methylated Guanine And Thioguanine Complexes, Kirsten Stinson, Michael Bowman Jun 2024

Computational Analysis Of O6-Methylated Guanine And Thioguanine Complexes, Kirsten Stinson, Michael Bowman

Lux et Fides: A Journal for Undergraduate Christian Scholars

DNA methylation occurring on the O6 position of guanine has been linked to the formation of cancer. DNA complexes with O6-methylated guanine have been studied experimentally, yet questions remain concerning the carcinogenic properties of O6-methylguanine. This present research explored the interaction between O6-methylguanine and its potential nucleobase pairs of cytosine and adenine in hopes of elucidating the mutagenic characteristics of O6-methylguanine. A variety of computational methods including Density Functional Theory (DFT), Symmetry Adapted Perturbation Theory (SAPT), Noncovalent Interaction (NCI) analysis, and Natural Bond Orbital (NBO) analysis were employed to comprehensively probe …


Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried Jul 2017

Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

Human O6-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O6-alkylguanine and O4-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein–protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ωave. We found …


Investigating The Mechanism Of Novel Anticancer Agent, As1411 : Does Metabolism To Guanine Play A Role?, Parker T Howard May 2017

Investigating The Mechanism Of Novel Anticancer Agent, As1411 : Does Metabolism To Guanine Play A Role?, Parker T Howard

College of Arts & Sciences Senior Theses

AS1411 is an oligonucleotide that has shown promising results in lab experiments and clinical trials as an anti-cancer drug, Likewise, treatments with guanine based purine compounds (GBPCs) have demonstrated similar anti-proliferative effects in vitro. This activity is dependent on the HGPRT enzyme. Similarities in activity and physical structure has led us to believe that AS1411 and GBPCs operate by a similar mechanism. To test this, we compare the activity of both in the presence of HGPRT siRNAs and HGPRT deficient cells. While siRNA treatment was unable to alter the activity of GBPCs or AS1411 in our cell lines, HGPRT deficient …


Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao May 2013

Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao

Dissertations and Theses (Open Access)

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with 99mTc and 68Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both 99mTc-N4amG and 99mTc-GP were stable up to 6 hours, whereas 68Ga-GP was stable up to 2 hours. Cell culture studies …