A5048935080- DNA and Nucleic Acid Chemistry
- DNA Repair Mechanisms
- Advanced biosensing and bioanalysis techniques
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Reactions
- RNA Research and Splicing
- Carcinogens and Genotoxicity Assessment
- Catalytic Cross-Coupling Reactions
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Synthesis and Catalytic Reactions
- Chemical Reaction Mechanisms
- Synthesis and Biological Evaluation
- RNA Interference and Gene Delivery
- Asymmetric Synthesis and Catalysis
- Viral Infections and Immunology Research
- RNA regulation and disease
- Chemical Synthesis and Analysis
Wave Life Sciences (United States)
2022-2023
Boehringer Ingelheim (United States)
2017-2021
University of Connecticut
2016-2020
Abstract Herein, we report the systematic investigation of stereopure phosphorothioate (PS) and phosphoryl guanidine (PN) linkages on siRNA-mediated silencing. The incorporation appropriately positioned configured PS PN to N-acetylgalactosamine (GalNAc)-conjugated siRNAs based multiple targets (Ttr HSD17B13) increased potency durability mRNA silencing in mouse hepatocytes vivo compared with reference molecules clinically proven formats. observation that same modification pattern had...
Abstract An efficient, sustainable, and broadly applicable procedure has been developed for Suzuki–Miyaura cross‐coupling reactions in environmentally benign solvent (water) by employing as little 500 ppm Pd(OAc) 2 with a monophosphorus BI‐DIME ligand the presence of inexpensive commercially available nonionic surfactant Triton X‐100. This method was applied to broad range functionalized reaction partners, thereby affording excellent yields coupling products, including active pharmaceutical...
The environmental pollutant 3-nitrobenzanthrone produces bulky aminobenzanthrone (ABA) DNA adducts with both guanine and adenine nucleobases. A major product occurs at the C8 position of (C8-dG-ABA). These present a strong block to replicative polymerases but, remarkably, can be bypassed in largely error-free manner by human Y-family polymerase η (hPol η). Here, we report crystal structure ternary Pol⋅DNA⋅dCTP complex between C8-dG-ABA-containing template:primer duplex hPol η. was captured...
The environmental pollutant 6-nitrochrysene (6-NC) is a potent mutagen and mammary carcinogen in rats. 6-NC the most ever tested newborn mouse assay. In mammalian cells, it metabolically activated by nitroreduction combination of ring oxidation pathways. pathway yields two major adducts with 2′-deoxyguanosine (dG), one at C8-position, N-(dG-8-yl)-6-AC, other exocyclic N2-position, 5-(dG-N2-yl)-6-AC. Here, we report total synthesis site-specific oligonucleotide containing 6-NC-derived C8 dG...
A mild and nonreversible tert-butylation of alcohols phenols can be achieved in high yields using the noncoordinating acid–base catalyst [bis(trifluoromethane)sulfonimide 2,6-lutidine] with a reagent, tert-butyl 2,2,2-trichloroacetimidate. This method allows use substrates containing acid sensitive groups such as ketal, Boc, boronate esters.
Abstract This unit describes the detailed procedure in five parts for synthesis of C8‐2′‐deoxyguanosine‐3‐aminobenzanthrone adduct located a desired site an oligonucleotide. The protected 2′‐deoxyguanosine, O 6 ‐benzyl‐ N 2 ‐DMTr‐3′‐5′‐bisTBDMS‐C8‐Br‐2′‐deoxyguanosine, is described first part. reduced carcinogen 3‐aminobenzanthrone part two. third outlines key step formation between and nucleoside by palladium‐catalyzed cross coupling reaction. final two describe phosphoramidite from...