180611-79-4Relevant academic research and scientific papers
An Excimer Clamp for Measuring Damaged-Base Excision by the DNA Repair Enzyme NTH1
Jun, Yong Woong,Wilson, David L.,Kietrys, Anna M.,Lotsof, Elizabeth R.,Conlon, Savannah G.,David, Sheila S.,Kool, Eric T.
supporting information, p. 7450 - 7455 (2020/03/23)
Direct measurement of DNA repair enzyme activities is important both for the basic study of cellular repair pathways as well as for potential new translational applications in their associated diseases. NTH1, a major glycosylase targeting oxidized pyrimidines, prevents mutations arising from this damage, and the regulation of NTH1 activity is important in resisting oxidative stress and in suppressing tumor formation. Herein, we describe a novel molecular strategy for the direct detection of damaged DNA base excision activity by a ratiometric fluorescence change. This strategy utilizes glycosylase-induced excimer formation of pyrenes, and modified DNA probes, incorporating two pyrene deoxynucleotides and a damaged base, enable the direct, real-time detection of NTH1 activity in vitro and in cellular lysates. The probe design was also applied in screening for potential NTH1 inhibitors, leading to the identification of a new small-molecule inhibitor with sub-micromolar potency.
Templated chemistry for monitoring damage and repair directly in duplex DNA
Lee, Seoung Ho,Wang, Shenliang,Kool, Eric T.
supporting information; experimental part, p. 8069 - 8071 (2012/09/21)
We report the fluorogenic detection of the product of base excision repair (an abasic site) in a specific sequence of duplex DNA. This is achieved by DNA-templated chemistry, employing triple helix-forming probes that contain unnatural nucleobases designed to selectively recognize the site of a missing base. Light-up signals of up to 36-fold were documented, and probes could be used to monitor enzymatic removal of a damaged base.
NOVEL NUCLEOSIDE ANALOGS WITH POLYCYCLIC AROMATIC GROUPS ATTACHED, METHODS OF SYNTHESIS AND USES THEREFOR
-
Page 12; 40, (2010/02/08)
The present invention provides fluorescent nucleosides carrying polycyclic aromatic hydrocarbons such as anthracene, phenanthrene, pyrene, stilbene, tetracene or pentacene. The subject nucleosides may be synthesized using a C-glycosidic bond formation met
Polycyclic aromatic DNA-base surrogates: High-affinity binding to an adenine-specific base-flipping DNA methyltransferase
Beuck, Christine,Singh, Ishwar,Bhattacharya, Anupam,Hecker, Walburga,Parmar, Virinder S.,Seitz, Oliver,Weinhold, Elmar
, p. 3958 - 3960 (2007/10/03)
Filling the hole is a strategy that confers high-affinity DNA binding to the M·TaqI DNA methyltransferase. Aromatic base surrogates (e.g. pyrene, red in picture) were introduced into DNA by means of organocuprate-mediated C-glycosylations. A new competitive binding assay revealed that DNA with aromatic base surrogates placed opposite to the target base binds to M·TaqI with up to 400-fold-enhanced affinity.
Local disruption of DNA-base stacking by bulky base surrogates
Singh, Ishwar,Hecker, Walburga,Prasad, Ashok K.,Parmar, Virinder S.,Seitz, Oliver
, p. 500 - 501 (2007/10/03)
A novel biphenyl base surrogate disrupts 2-aminopurine base stacking while maintaining duplex integrity.
Naphthalene, phenanthrene, and pyrene as DNA base analogues: Synthesis, structure, and fluorescence in DNA
Ren, Rex X.-F.,Chaudhuri, Narayan C.,Paris, Pamela L.,Rumney IV, Squire,Kool, Eric T.
, p. 7671 - 7678 (2007/10/03)
We describe the synthesis, structures, and DNA incorporation of deoxyribonucleosides carrying polycyclic aromatic hydrocarbons as the DNA 'base' analogue. The new polycyclic compounds are 1-naphthyl, 2-naphthyl, 9-phenanthrenyl, and 1-pyrenyl deoxynucleos
