A5070495967- DNA and Nucleic Acid Chemistry
- Carcinogens and Genotoxicity Assessment
- DNA Repair Mechanisms
- Synthesis and Biological Evaluation
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Bacteriophages and microbial interactions
- Quinazolinone synthesis and applications
- Enzyme Structure and Function
- Polymer crystallization and properties
- RNA Research and Splicing
University of Lethbridge
2015-2023
Abstract A set of >300 nonredundant high-resolution RNA–protein complexes were rigorously searched for π-contacts between an amino acid side chain (W, H, F, Y, R, E and D) RNA nucleobase (denoted π–π interaction) or ribose moiety sugar–π). The resulting dataset >1500 visually inspected classified based on the interaction type, acids components involved. More than 80% structures contained at least one π-interaction, with contacts making up 59% identified interactions. sugar–π...
There were 1765 contacts identified between DNA nucleobases or deoxyribose and cyclic (W, H, F, Y) acyclic (R, E, D) amino acids in 672 X-ray structures of DNA–protein complexes. In this first study to compare π-interactions the acids, visual inspection was used categorize acid interactions as nucleobase π–π (according biological edge) sugar–π sugar edge). Overall, 54% are interactions, which involve all but more common for Y, R, with similar frequencies. Among binding arrangements, prefer...
Human exposure to aromatic amines (AAs) can result in carcinogenic DNA adducts. To complement previous work geared toward understanding the mutagenicity of AA-derived adducts, which has almost exclusively studied (monoadducted) containing a single lesion, present provides first in-depth comparison structure monoadducted and diadducted duplexes. Specifically, molecular dynamics (MD) simulations were initially performed on nonmutagenic single-ringed N-(deoxyguanosin-8-yl)-aniline (ANdG) or...
Aromatic chemical carcinogens can undergo enzymatic transformations to produce a range of electrophilic species that attach covalently the C8-site 2'-deoxyguanosine (dG) afford C8-dG adducts. The most studied adducts are formed from arylamines and contain N-linkage separating dG C8-aryl moiety. Other carcinogenic result in direct aryl ring attachment moiety, resulting C-linked have reduced conformational flexibility compared corresponding N-linked adducts, which alter their orientation DNA...
The present work investigates the effects of size and shape nitrogen-containing aromatic (NCA) skeleton on structure DNA damaged through adduct formation at C8 2'-deoxyguanosine (dG), a common lesion associated with chemical carcinogenesis. Specifically, density functional theory (DFT) calculations (B3LYP-D3) molecular dynamics (MD) simulations (AMBER) are performed seven model adducts systematic expansion NCA moiety. DFT reveal that moiety affects nucleobase-carcinogen linkage....
Nitroaromatic compounds represent a major class of industrial chemicals that are also found in nature. Polycyclic derivatives regarded as potent mutagens and carcinogens following bioactivation to produce nitrenium electrophiles covalently modify DNA afford N-linked C8-2′-deoxyguanosine (C8-dG) lesions can induce frameshift mutations, especially CpG repeat sequences. In contrast, their monocyclic counterparts typically exhibit weak mutagenicity or lack thereof, despite undergoing C8-dG...
Chemical alkylation of DNA produces potentially toxic and mutagenic damage such as O 6 ‐alkylguanine ( ‐alkylG) adducts. Non‐natural nucleoside analogues that pair with adducts provide a potential basis for studying damaged . Herein, we evaluated the base pairing properties elongated containing napthalene‐derived tricyclic nucleobases adduct‐pairing in hybridization probes. duplex melting studies revealed analogs formed more stable pairs opposite ‐alkylG than G were better able to...
Exposure of humans to carcinogenic aromatic amines (AAs) occurs daily. AAs are bioactivated in cells into products that attack DNA, primarily leading N-linked C8-dG adducts. Previous work on DNA containing a single AA-derived adduct (monoadducted DNA) has shown structure-function relationship between the damaged conformation and cellular outcomes. However, relatively little is known about biological outcomes two bulky adducts (diadducted close proximity. To fill this current void literature,...
DNA is damaged through various exogenous sources (e.g., automobile exhaust, tobacco smoke, and processed foods), which can yield diverse C8-dG bulky aryl adducts. Adducts are known to induce structural changes that lead biological outcomes, ranging from cell death diseases such as cancer. Unfortunately, the relationship between chemical composition of product, adducted structure, consequences not well understood, limits development disease detection prevention strategies. The present study...