115044-77-4

Upstream product

• 18552-90-4 6-chloro-2-iodo-(9H)-purine 
• 1621101-38-9 6-chloro-2-iodo-9-[(2’-O-acetyl-3’-deoxy-5’-O-(4-methylbenzoyl))-β-D-ribofuranosyl]purine 
• 142823-65-2 1,2-di-O-acetyl-3-deoxy-5-O-(4-methylbenzoyl)-D-α,β-xylofuranose 
• 133519-48-9 9-[3',5'-bis-O-(tert-butyldimethylsilyl)-2-deoxy-β-D-erythro-pentofuranosyl]-6-chloro-2-iodopurine 
• 2004-07-1 2-Amino-6-chloropurine riboside 
• 133519-50-3 2-iodo-9-[3-deoxy-2,5-O-bis-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]adenine 

Relevant academic research and scientific papers

Synthetic approaches to new doubly modified nucleosides: Congeners of cordycepin and related 2'-deoxyadenosine

The syntheses of novel analogues of cordycepin (compounds 20-25) and 2'-deoxyadenosine (compounds 11, 13-15, 18, 19) are reported. In order to obtain entry into both the 3'-deoxy and 2'-deoxy isomeric series from a common starting compound, 2-amino-6-chloropurine ribonucleoside, this precursor was protected by conversion to a mixture of 2',5'- and 3',5'-bis-silyl compounds prior to modifications at the 2'- or 3'- positions of the carbohydrate moiety and the 2-position of the base component. Observation of silyl group isomerization is discussed. The other key transformations in the syntheses were radical deoxygenations (carbohydrate moiety), radical iodinations (tailoring of base for modification), and metal-mediated functionalization reactions (regio-specific modifications of base component). Structures of the final target molecules and their purities were established by UV, high-field 1H and 13C NMR, and FAB HRMS data. The synthetic approaches presented have generality and provide entry into a variety of doubly modified nucleosides.

Chain-terminating and clickable NAD+ analogues for labeling the target proteins of ADP-ribosyltransferases

ADP-ribosyltransferases (ARTs) use NAD+ as a substrate and play important roles in numerous biological processes, such as the DNA damage response and cell cycle regulation, by transferring multiple ADP-ribose units onto target proteins to form poly(ADP-ribose) (PAR) chains of variable sizes. Efforts to identify direct targets of PARylation, as well as the specific ADP-ribose acceptor sites, must all tackle the complexity of PAR. Herein, we report new NAD+ analogues that are efficiently processed by wild-type ARTs and lead to chain termination owing to a lack of the required hydroxy group, thereby significantly reducing the complexity of the protein modification. Due to the presence of an alkyne group, these NAD+ analogues allow subsequent manipulations by click chemistry for labeling with dyes or affinity markers. This study provides insight into the substrate scope of ARTs and might pave the way for the further developments of chemical tools for investigating PAR metabolism.