التفاصيل البيبلوغرافية
| العنوان: |
Efficient Synthesis of DNA Duplexes Containing Reduced Acetaldehyde Interstrand Cross-Links |
| المؤلفون: |
Sally B. Morton (14312875), L. David Finger (14312878), Roxanne van der Sluijs (14312881), William D. Mulcrone (14312884), Michael Hodskinson (14312887), Christopher L. Millington (3072237), Christina Vanhinsbergh (14312890), Ketan J. Patel (14312893), Mark J. Dickman (1893028), Puck Knipscheer (14312896), Jane A. Grasby (2264884), David M. Williams (16225) |
| سنة النشر: |
2022 |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Cell Biology, Genetics, Molecular Biology, Cancer, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Physical Sciences not elsewhere classified, yield upon incubation, stable reduced form, potentially lethal events, involved lengthy post, bone marrow failure, linked duplex displayed, prevent dna replication, 2 ′- deoxyinosine, reduced icl using, show using, duplex resulting, yielding approach, vivo <, room temperature, reaction forms, r <, proteins within, previous routes, opposite strands, n < |
| الوصف: |
DNA interstrand cross-links (ICLs) prevent DNA replication and transcription and can lead to potentially lethal events, such as cancer or bone marrow failure. ICLs are typically repaired by proteins within the Fanconi Anemia (FA) pathway, although the details of the pathway are not fully established. Methods to generate DNA containing ICLs are key to furthering the understanding of DNA cross-link repair. A major route to ICL formation in vivo involves reaction of DNA with acetaldehyde, derived from ethanol metabolism. This reaction forms a three-carbon bridged ICL involving the amino groups of adjacent guanines in opposite strands of a duplex resulting in amino and imino functionalities. A stable reduced form of the ICL has applications in understanding the recognition and repair of these types of adducts. Previous routes to creating DNA duplexes containing these adducts have involved lengthy post-DNA synthesis chemistry followed by reduction of the imine. Here, an efficient and high-yielding approach to the reduced ICL using a novel N 2 -(( R )-4-trifluoroacetamidobutan-2-yl)-2′-deoxyguanosine phosphoramidite is described. Following standard automated DNA synthesis and deprotection, the ICL is formed overnight in over 90% yield upon incubation at room temperature with a complementary oligodeoxyribonucleotide containing 2-fluoro-2′-deoxyinosine. The cross-linked duplex displayed a melting transition 25 °C higher than control sequences. Importantly, we show using the Xenopus egg extract system that an ICL synthesized by this method is repaired by the FA pathway. The simplicity and efficiency of this methodology for preparing reduced acetaldehyde ICLs will facilitate access to these DNA architectures for future studies on cross-link repair. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/journal_contribution/Efficient_Synthesis_of_DNA_Duplexes_Containing_Reduced_Acetaldehyde_Interstrand_Cross-Links/21799459Test |
| DOI: |
10.1021/jacs.2c10070.s001 |
| الإتاحة: |
https://doi.org/10.1021/jacs.2c10070.s001Test |
| حقوق: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.69CCD0CF |
| قاعدة البيانات: |
BASE |
