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Cyanine Dyes Targeting G-quadruplex DNA: Significance in Sequence and Conformation SelectivityHuynh, Hang T 16 December 2015 (has links)
Small molecules interacting with DNA is an emerging theme in scientific research due to its specificity and minimal side-effect. Moreover, a large amount of research has been done on finding compounds that can stabilize G-quadruplex DNA, a non-canonical secondary DNA structure, to inhibit cancerous cell proliferation. G-quadruplex DNA is found in the guanine-rich region of the chromosome that has an important role in protecting chromosomes from unwinding, participate in gene expression, contribute in the control replication of cells and more. In this research, rationally designed, synthetic cyanine dye derivatives, which were tested under physiologically relevant conditions, were found to selectively bind to G-quadruplex over duplex DNA and are favored to one structure over another. The interactions were observed using UV-Vis thermal melting, fluorescence titration, circular dichroism titration, and surface plasmon resonance analysis. For fluorescence and selectivity properties, cyanine dyes, therefore, have the potential to become the detections and/or therapeutic drugs to target cancers and many other fatal diseases.
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Stabilization of a Bimolecular Triplex by 3′-S-Phosphorothiolate Modifications: An NMR and UV Thermal Melting InvestigationEvans, K., Bhamra, I., Wheelhouse, Richard T., Arnold, J.R.P., Cosstick, R., Fisher, J. January 2015 (has links)
Yes / Triplexes formed from oligonucleic acids are key to a number of biological processes. They have attracted attention as molecular biology tools and as a result of their relevance in novel therapeutic strategies. The recognition properties of single-stranded nucleic acids are also relevant in third-strand binding. Thus, there has been considerable activity in generating such moieties, referred to as triplex forming oligonucleotides (TFOs). Triplexes, composed of Watson–Crick (W–C) base-paired DNA duplexes and a Hoogsteen base-paired RNA strand, are reported to be more thermodynamically stable than those in which the third strand is DNA. Consequently, synthetic efforts have been focused on developing TFOs with RNA-like structural properties. Here, the structural and stability studies of such a TFO, composed of deoxynucleic acids, but with 3′-S-phosphorothiolate (3′-SP) linkages at two sites is described. The modification results in an increase in triplex melting temperature as determined by UV absorption measurements. 1H NMR analysis and structure generation for the (hairpin) duplex component and the native and modified triplexes revealed that the double helix is not significantly altered by the major groove binding of either TFO. However, the triplex involving the 3′-SP modifications is more compact. The 3′-SP modification was previously shown to stabilise G-quadruplex and i-motif structures and therefore is now proposed as a generic solution to stabilising multi-stranded DNA structures.
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Cyanine Dye Interactions with Quadruplex and Duplex DNA: Changes in Conformation, Stability, and AffinityMickelson, Leah E 17 June 2011 (has links)
There is a high demand for quadruplex-specific compounds that not only bind preferentially to quadruplex DNA over duplex DNA, but also bind to one quadruplex motif over other motifs. Quadruplex structures are recognized as common occurrences in cancer cells, and if a compound could stabilize this structure, it may serve as an effective anti-cancer treatment with minimal side effects. In this study, cyanine dyes’ interactions with DNA were analyzed with fluorescence titrations, UV-Vis thermal studies, circular dichroism titrations, and surface plasmon resonance (SPR) analysis. With these techniques, binding affinity, DNA stabilization, and conformational shifts were analyzed to determine if cyanine dyes could act as quadruplex-specific binding compounds for possible cancer treatments.
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Identifying subarctic river thermal and mechanical ice break-up using seismic sensingUrsica, Stefania January 2021 (has links)
River-ice break-up in high-latitude regions, despite its brevity, is a fundamental process, representing the most dynamic and complex period of fluvial processes. Moreover, ice break-up has significant cascading ecological effects, with a different severity for mechanical vs. thermal break-up, and thus, motivates the importance of monitoring efforts. Classical research methods, such as fieldwork or analysis of photographs and aerial imagery, offer a general perspective on the timing of ice break-up but have safety and logistic issues caused by the dangers of unstable ice cover, the lag times between event occurrence and observation, and the frequent low visibilities. The emerging field of environmental seismology, which studies surface processes through seismic signals, provides an alternative solution to these shortcomings by continuously recording high temporal resolution data. Seismic sensing can potentially record any event within a set distance if the produced signal is powerful enough. Three geophones had monitored the subarctic Sävar River reach for 185 days to test the efficiency of seismic methods to capture ice-cracking events, and based on their characteristics, to identify thermal vs. mechanical ice break-up. With visual and multivariate analysis, seismic methods provided a conservative set of 2 228 events, detected at milliseconds precision, described, and located. Besides, both trigger lag times and principal component analysis depicted correlations between environmental drivers and ice-cracking events. The automatic picker based on duration and trigger thresholds required manual supervision because of the initial numerous false signals that accounted for 96% of total initial events. Ice-cracking signals as short as 0.2s and frequencies of 8-40 Hz with an average power of -117 dB were statistically defined, classified, and described by case events as two types, associated, based on their spectral and temporal patterns, with the two ice break-up modes. With an estimated Rayleigh wave velocity of 680 m/s, all ice-cracking signals' locations were within the instrumented area. Trigger lag times analysis improved detection and showed a strong link between ice-cracking events and drivers of lag times less than three hours, including near-immediate responses (< 2s). With multivariate analysis, the lag times showed a mainly climatic control for thermal melting and a primarily fluvial control in mechanical ice break-up. The combination of statistical and seismic analysis provides, despite the considerable manual screening, a valid and potentially site-transferable method to extract and describe ice-cracking signals and thus identify ice break-up modes in northern rivers.
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