Targeting Telomerase via Its Key RNA/DNA Heteroduplex

Francis, Rawle; West, Corinna; Friedman, Simon H.

doi:10.1006/bioo.2000.1196

Cited by 23 publications

(18 citation statements)

References 13 publications

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“…The angiogenic activity of cheiradone was determined using the semi-quantitative chick chorioallantoic assay (CAM) as described previously [36]. To expose the CAM a window was created in the shells of 4 day-old chicken eggs.…”

Section: Methodsmentioning

confidence: 99%

Cheiradone: a vascular endothelial cell growth factor receptor antagonist

et al. 2008

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Background: Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with physiological (for example wound healing) and pathological conditions (tumour development). Vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) are the major angiogenic regulators. We have identified a natural product (cheiradone) isolated from a Euphorbia species which inhibited in vivo and in vitro VEGFstimulated angiogenesis but had no effect on FGF-2 or EGF activity. Two primary cultures, bovine aortic and human dermal endothelial cells were used in in vitro (proliferation, wound healing, invasion in Matrigel and tube formation) and in vivo (the chick chorioallantoic membrane) models of angiogenesis in the presence of growth factors and cheiradone. In all cases, the concentration of cheiradone which caused 50% inhibition (IC 50 ) was determined. The effect of cheiradone on the binding of growth factors to their receptors was also investigated.

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Section: Methodsmentioning

confidence: 99%

Cheiradone: a vascular endothelial cell growth factor receptor antagonist

et al. 2008

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“…The tumour-specific enzyme, telomerase is a specialized reverse transcriptase, with protein structure domains closely-related to the HIV enzyme (6). A DNA·RNA hybrid duplex is generated in the course of the telomerase reaction, so telomerase is also amenable to such a small-molecule targeting strategy (7, 8). Indeed, the thermodynamic stability of the DNA-RNA hybrid appears to regulate telomerase activity (9).…”

Section: Introductionmentioning

confidence: 99%

Drug Binding to DNA⋅RNA Hybrid Structures

Wheelhouse¹,

Chaires²

2009

Methods in Molecular Biology

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SummaryDNA·RNA hybrid duplexes are functionally important structures in gene expression that are underutilized as potential drug targets. Several tools are described here for the discovery and characterization of small molecules capable of the selective recognition of DNA·RNA hybrid structures. Competition dialysis and thermal denaturation of mixtures of polynucleotide structures can be used to identify small molecules that bind selectively to DNA·RNA hybrids. An assay that measures small molecule inhibition of RNase H can be used to measure a functional response to these ligands.

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“…Previously, we have developed a strategy to inhibit telomerase by targeting small molecules to the RNA/DNA duplex that forms during telomerase’s catalytic cycle. 1 This duplex forms when the template portion of telomerase’s RNA subunit binds to the telomeric DNA, acting as a template for the DNA’s extension. The rationale behind our approach is that molecules that bind this duplex, e.g.…”

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confidence: 99%