56973-12-7

Usage

InChI:InChI=1/C11H15N5O4/c1-4-15-6-9(12)13-3-14-10(6)16(4)11-8(19)7(18)5(2-17)20-11/h3,5,7-8,11,17-19H,2H2,1H3,(H2,12,13,14)/t5-,7-,8-,11-/m1/s1

Upstream product

• 110526-63-1 2',3',5'-tris-O-(tert-butyldimethylsilyl)-8-methyladenosine 
• 75-24-1 trimethylaluminum 
• 2946-39-6 8-bromoadenosine 
• 594-27-4 tetramethylstannane 
• 64911-28-0 O^2'_,O3'_,O5'-tris-(tert-butyl-dimethyl-silanyl)-adenosine 
• 69359-30-4 5'-O-acetyl-8-ethoxycarbonylmethyl-2',3'-O-isopropylideneadenosine 
• 69359-29-1 5'-O-acetyl-2',3'-O-isopropylidene-8-methylsulfonyladenosine 
• 58-61-7 adenosine 
• 107-71-1 tert-butyl peroxyacetate 
• 65627-13-6 2',3'-O-isopropylidene-8-methyladenosine 

Downstream Products

• 68045-12-5 8-methyladenosine 5'-monophosphate 

Relevant academic research and scientific papers

Synthesis of cyclic adenosine 5′-diphosphate ribose analogues: A C2′ endo/syn "southern" ribose conformation underlies activity at the sea urchin cADPR receptor

Novel 8-substituted base and sugar-modified analogues of the Ca 2+ mobilizing second messenger cyclic adenosine 5′-diphosphate ribose (cADPR) were synthesized using a chemoenzymatic approach and evaluated for activity in sea urchin egg homogenate (SUH) and in Jurkat T-lymphocytes; conformational analysis investigated by 1H NMR spectroscopy revealed that a C2′ endo/syn conformation of the "southern" ribose is crucial for agonist or antagonist activity at the SUH-, but not at the T cell-cADPR receptor.

RImN and Cfr are Radical SAM Enzymes Involved in Methylation of Ribosomal RNA

Posttranscriptional modifications of ribosomal RNA (rRNA) nucleotides are a common mechanism of modulating the ribosome's function and conferring bacterial resistance to ribosome-targeting antibiotics. One such modification is methylation of an adenosine nucleotide within the peptidyl transferase center of the ribosome mediated by the endogenous methyltransferase RImN and its evolutionarily related resistance enzyme Cfr. These methyltransferases catalyze methyl transfer to aromatic carbon atoms of the adenosine within a complex 23S rRNA substrate to form the 2,8-dimethylated product. RImN and Cfr are members of the Radical SAM superfamily and contain the characteristic cysteine-rich CX3CX2C motif. We demonstrate that both enzymes are capable of accommodating the requisite [4Fe-4S] cluster. S-Adenosylmethionine (SAM) is both the methyl donor and the source of a 5′-deoxyadenosyl radical, which activates the substrate for methylation. Detailed analyses of the rRNA requirements show that the enzymes can utilize proteinfree 23S rRNA as a substrate, but not the fully assembled large ribosomal subunit, suggesting that the methylations take place during the assembly of the ribosome. The key recognition elements in the 23S rRNA are helices 90-92 and the adjacent single stranded RNA that encompasses A2503. To our knowledge, this study represents the first in vitro description of a methyl transfer catalyzed by a member of the Radical SAM superfamily, and it expands the catalytic repertoire of this diverse enzyme class. Furthermore, by providing information on both the timing of methylation and its substrate requirements, our findings have important implications for the functional consequences of Cfr-mediated modification of rRNA in the acquisition of antibiotic resistance.

New insights into the design of inhibitors of human S-adenosylmethionine decarboxylase: studies of adenine C8 substitution in structural analogues of S-adenosylmethionine

S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution would be more potent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituents at the 8-position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. The biochemical analysis indicated that an 8-methyl substituent resulted in more potent inhibitors, yet most other 8-substitutions provided no benefit over the parent compound. To understand these results, we used computational modeling and X-ray crystallography to study C8-substituted adenine analogues bound in the active site.

INHIBITORS OF S-ADENOSYL-L-METHIONINE DECARBOXYLASE

Novel mechanism-based inhibitors of S-adenosyl-L-methionine decarboxylase are provided. These compounds of formula (1) inhibit the life cycle of trypanosomes, and are useful to treat subjects infected with African trypanosomes. The invention includes pharmaceutical compositions and methods of using the compounds of formula (1).

PURINE NUCLEOTIDE DERIVATIVES

This invention provides novel 8-carbyl substituted cAMPS and a novel procedures for the preparation of 8-Br-cAMP, a key starting material.

Antiviral Activity of C-Alkylated Purine Nucleosides Obtained by Cross-Coupling with Tetraalkyltin Reagents

2-, 6-, And 8-alkylated (methyl, ethyl, and vinyl) adenosine analogues were synthesized by a palladium-catalyzed cross-coupling of a tetraalkyltin with the halogenated purine nucleosides.The synthesis of the 8-substituted analogues was accomplished using a transient protection procedure.The 6-alkylated-9-β-D-ribofuranosylpurines as well as 2-ethyladenosine were cytotoxic at relatively low concentrations (0.8-10 μg/mL). 8-Methyladenosine was a potent and selective inhibitor of vaccinia virus, whereas 8-ethyl- and 8-vinyladenosine were specifically inhibitory to respiratory syncytial virus. 8-Vinyladenosine displayed particular activity against herpes simplex virus (type 1).

Straightforward C-8 alkylation of adenosine analogues with tetraalkyltin reagents

A one step synthesis of the 8-methyl-, 8-ethyl- and 8-vinyl derivatives of adenosine, 2'-deoxyadenosine and 2',3'-dideoxyadenosine starting from the readily available 8-bromo congeners is described. This reaction makes use of a transient silylation procedure and a Pd(0) catalysed cross-coupling with tetraorganotin reagents.