67805-97-4

Upstream product

• 58-61-7 adenosine 
• 892-48-8 5'-deoxy-5'-chloroadenosine 
• 14031-35-7 S-Adenosyl-L-methionine 
• 362-75-4 2',3'-isopropylidene adenosine 
• 84365-04-8 5'-acetylthio-5'-deoxy-2',3'-O-isopropylidene adenosine 
• 139361-69-6 5'-acetylthio-5'-deoxyadenosine 
• 132628-18-3 (2R,3R,4S,5S)-2-(6-Amino-purin-9-yl)-5-[9-(4-methoxy-phenyl)-9H-xanthen-9-ylsulfanylmethyl]-tetrahydro-furan-3,4-diol 

Downstream Products

• 1186091-85-9 Ditiazofurin disulfide 
• 1186091-86-0 Tiazofurin adenosine disulfide 
• 5256-83-7 Diadenosine disulfide 
• 1186091-92-8 8-Bromoadenosine adenosine disulfide 
• 1186091-93-9 Di(8-bromoadenosine) disulfide 

Relevant academic research and scientific papers

Inactivation of S-adenosyl-L-homocysteine hydrolase with novel 5′-thioadenosine derivatives. Antiviral effects

Synthesis of 5′-S-vinyl-5′-thioadenosine 5, 5′-S-ethynyl-5′-thioadenosine 7 and 5′-S-cyano-5′-thioadenosine 9 is described. Incubation of AdoHcy hydrolase with 5, 7 and 9 resulted in time- and concentration-dependent inactivation of the enzyme and partial depletion of its NAD+ content. From these results and characterisation of metabolites released during the inactivation process, hypothetical mechanisms are suggested. The antiviral activity of 5, 7 and 9 was examined. Significant activities were noted with 5 against Vaccinia, Junin and Taccaribe viruses.

The Catalytic Mechanism of the Class C Radical S-Adenosylmethionine Methyltransferase NosN

S-Adenosylmethionine (SAM) is one of the most common co-substrates in enzyme-catalyzed methylation reactions. Most SAM-dependent reactions proceed through an SN2 mechanism, whereas a subset of them involves radical intermediates for methylating non-nucleophilic substrates. Herein, we report the characterization and mechanistic investigation of NosN, a class C radical SAM methyltransferase involved in the biosynthesis of the thiopeptide antibiotic nosiheptide. We show that, in contrast to all known SAM-dependent methyltransferases, NosN does not produce S-adenosylhomocysteine (SAH) as a co-product. Instead, NosN converts SAM into 5′-methylthioadenosine as a direct methyl donor, employing a radical-based mechanism for methylation and releasing 5′-thioadenosine as a co-product. A series of biochemical and computational studies allowed us to propose a comprehensive mechanism for NosN catalysis, which represents a new paradigm for enzyme-catalyzed methylation reactions.

Tryptophan Lyase (NosL): A Cornucopia of 5′-Deoxyadenosyl Radical Mediated Transformations

Tryptophan lyase (NosL) is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the formation of 3-methyl-2-indolic acid from l-tryptophan. In this paper, we demonstrate that the 5′-deoxyadenosyl radical is considerably more versatile in its chem

Selective inhibition of nicotinamide adenine dinucleotide kinases by dinucleoside disulfide mimics of nicotinamide adenine dinucleotide analogues

Diadenosine disulfide (5) was reported to inhibit NAD kinase from Lysteria monocytogenes and the crystal structure of the enzyme-inhibitor complex has been solved. We have synthesized tiazofurin adenosine disulfide (4) and the disulfide 5, and found that these compounds were moderate inhibitors of human NAD kinase (IC50 = 110 μM and IC50 = 87 μM, respectively) and Mycobacterium tuberculosis NAD kinase (IC50 = 80 μM and IC50 = 45 μM, respectively). We also found that NAD mimics with a short disulfide (-S-S-) moiety were able to bind in the folded (compact) conformation but not in the common extended conformation, which requires the presence of a longer pyrophosphate (-O-P-O-P-O-) linkage. Since majority of NAD-dependent enzymes bind NAD in the extended conformation, selective inhibition of NAD kinases by disulfide analogues has been observed. Introduction of bromine at the C8 of the adenine ring restricted the adenosine moiety of diadenosine disulfides to the syn conformation making it even more compact. The 8-bromoadenosine adenosine disulfide (14) and its di(8-bromoadenosine) analogue (15) were found to be the most potent inhibitors of human (IC50 = 6 μM) and mycobacterium NAD kinase (IC50 = 14-19 μΜ reported so far. None of the disulfide analogues showed inhibition of lactate-, and inosine monophosphate-dehydrogenase (IMPDH), enzymes that bind NAD in the extended conformation.

Method for Identifying Inhibitors Using a Homology Model of Polo-Like Kinase 1

The present invention relates to a homology model for PLK, and the use thereof in assays for the identification of small molecule PLK modulators. The invention further relates to PLK modulators identified by said assays, and their use in the treatment of PLK-related disorders such as proliferative disorders.

Efficient synthesis of s-adenosyl-L-homocysteine natural product analogues and their use to elucidate the structural determinant for cofactor binding of the DNA methyltransferase M·HhaI

5'-Acetylthio-5'-deoxy-2',3'-O-isopropylideneadenosine (8) was directly prepared from commercially available 2',3'-O-isopropylideneadenosine (7) and thioacetic acid under Mitsunobu conditions in almost quantitative yield. In situ cleavage of the acetylthio function of 8 followed by coupling with different alkyl bromides proceeded with high yields. Deprotection of the obtained 5'-thionucleosides yielded the S-adenosyl-L-homocysteine analogues decarboxylated AdoHcy (11), deaminated AdoHcy (14) and 5'- [3(cyano)propylthio]-5'-deoxyadenosine (16) in good overall yields. Direct deprotection of the thionucleoside 8 delivered 5'-thio-5'-deoxyadenosine (18) in excellent yield. In addition, binding constants of these AdoHcy analogues and the DNA methyltransferase M·HhaI were determined in a fluorescence assay.

9-(4-METHOXYPHENYL)XANTHEN-9-THIOL: A USEFUL REAGENT FOR THE PREPARATION OF THIOLS

Treatment of 5'-chloro-5'-deoxynucleosides (5) with the conjugate base of 9-(4-methoxyphenyl)xanthen-9-thiol (3b), followed by acid-promoted removal of the 5'-S- group in the presence of pyrrole gives the corresponding 5'-deoxy-5'-mercaptonucleosides (7) in good yields.