Mitomycin C (MC) an antitumor drug and decarbamoylmitomycin C (DMC), a derivative of MC lacking the carbamoyl moiety, are DNA alkylating agents which can form DNA interstrand crosslinks (ICLs) between deoxyguanosine residues located on opposing DNA strands. MC forms primarily deoxyguanosine adducts with a 1"-R stereochemistry at the guanine-mitosene bond (1"-α, trans) whereas DMC forms mainly adducts with a 1"-S stereochemistry (1"-β, cis). The crosslinking reaction is diastereospecific: trans-crosslinks are formed exclusively at CpG sequences, while cis-crosslinks are formed only at GpC sequences. Until now, oligonucleotides containing 1"-β-deoxyguanosine adducts or ICL at a specific site could not be synthesized, thus limiting the investigation of the role played by the stereochemical configuration at C1'' in the toxicity of these compounds. Here, a novel biomimetic synthesis to access these substrates is presented. Structural proof of the adducted oligonucleotides and ICL were provided by enzymatic digestion to nucleosides, high resolution mass spectral analysis, CD spectroscopy and UV melting temperature studies. Finally, a virtual model of the 25-mer 1"-β ICL synthesized was created to explore the conformational space and structural features of the crosslinked duplex.
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http://dx.doi.org/10.1002/chem.202002452 | DOI Listing |
Mikrochim Acta
January 2025
School of Public Health, Jilin University, Changchun, Jilin, 130021, P. R. China.
A spherical nucleic acid (SNA, AuNPs-aptamer) into CRISPR/Cas12a system combined with poly T-template copper nanoparticles as fluorescence reporter was fabricated to establish an amplification-free sensitive method for Staphylococcus aureus (S. aureus) detection. This method, named PTCas12a, utilizes the concept that the bifunction of SNA recognizes the S.
View Article and Find Full Text PDFSci Rep
January 2025
School of Public Health, Jining Medical University, Jining, 272067, People's Republic of China.
Aptamers have shown potential for diagnosing clinical markers and targeted treatment of diseases. However, their limited stability and short half-life hinder their broader applications. Here, a real sample assisted capture-SELEX strategy is proposed to enhance the aptamer stability, using the selection of specific aptamer towards PD-L1 as an example.
View Article and Find Full Text PDFMikrochim Acta
January 2025
College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
An innovative colorimetric sensing strategy was developed for the detection of glucose by the integration of glucose aptamer, glucose oxidase (GOx), and horseradish peroxidase (HRP), termed aptamer proximal enzyme cascade reactions (APECR). In the presence of glucose, aptamer binding enables GOx to catalyze glucose oxidation into HO efficiently. Subsequently, the adjacent HRP catalyzes the oxidation of the peroxidase substrate, 2,2'-biazobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), utilizing the generated HO, resulting in a distinct color change.
View Article and Find Full Text PDFMar Biotechnol (NY)
January 2025
School of Marine Science and Technology, Harbin Institute of Technology (Weihai), Wenhua West Road, 2#, Weihai, 264209, People's Republic of China.
Recently, the scale and frequency of harmful algae blooms (HABs) have gradually increased, posing a serious threat to human health, marine ecosystems and economic development. For early warning, a method is required that can quickly detect and monitor microalgae. It is proposed to use aptamer targeted to Prorocentrum minimum, along with exonuclease III (Exo III), gold nanoparticles, target single-stranded DNA and hairpin structure probe to construct a new method, i.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Chemistry, Boston College, Chestnut Hill, MA, USA.
Recent advances in gene editing and precise regulation of gene expression based on CRISPR technologies have provided powerful tools for the understanding and manipulation of gene functions. Fusing RNA aptamers to the sgRNA of CRISPR can recruit cognate RNA-binding protein (RBP) effectors to target genomic sites, and the expression of sgRNA containing different RNA aptamers permit simultaneous multiplexed and multifunctional gene regulations. Here, we report an intracellular directed evolution platform for RNA aptamers against intracellularly expressed RBPs.
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