53-83-8Relevant academic research and scientific papers
Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis
Fateev, Ilja V.,Sinitsina, Ekaterina V.,Bikanasova, Aiguzel U.,Kostromina, Maria A.,Tuzova, Elena S.,Esipova, Larisa V.,Muravyova, Tatiana I.,Kayushin, Alexei L.,Konstantinova, Irina D.,Esipov, Roman S.
, p. 3098 - 3105 (2019/01/21)
Phosphoribosyltransferases are the tools that allow the synthesis of nucleotide analogues using multi-enzymatic cascades. The recombinant adenine phosphoribosyltransferase (TthAPRT) and hypoxanthine phosphoribosyltransferase (TthHPRT) from Thermus thermophilus HB27 were expressed in E.coli strains and purified by chromatographic methods with yields of 10-13 mg per liter of culture. The activity dependence of TthAPRT and TthHPRT on different factors was investigated along with the substrate specificity towards different heterocyclic bases. The kinetic parameters for TthHPRT with natural substrates were determined. Two nucleotides were synthesized: 9-(β-D-ribofuranosyl)-2-chloroadenine 5'-monophosphate (2-l-AMP) using TthAPRT and 1-(β-Dribofuranosyl)pyrazolo[3,4-d]pyrimidine-4-one 5'-monophosphate (Allop-MP) using TthPRT.
Aberrant cyclization affords a C-6 modified cyclic adenosine 5′-diphosphoribose analogue with biological activity in Jurkat T cells
Moreau, Christelle,Kirchberger, Tanja,Zhang, Bo,Thomas, Mark P.,Weber, Karin,Guse, Andreas H.,Potter, Barry V. L.
, p. 1478 - 1489 (2012/04/23)
Two nicotinamide adenine dinucleotide (NAD+) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD+ (6-N-methyl nicotinamide adenosine 5′-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5′-diphosphoribose, 11), whereas 6-thio NHD+ (nicotinamide 6-mercaptopurine 5′-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5′-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5′-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1-cIDPR-induced Ca2+ release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5′-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1-cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling.
Five-component cascade synthesis of nucleotide analogues in an engineered self-immobilized enzyme aggregate
Scism, Robert A.,Bachmann, Brian O.
scheme or table, p. 67 - 70 (2010/10/20)
(Chemical Equation Presented) Pathway in a particle: A five-enzyme biosynthetic pathway was self-immobilized to form a single biocatalyst for generation of purine nucleotide analogues from d-ribose. This method provides an alternative to engineering biosynthetic pathways in whole cells that obviates problems associated with toxicity, transport and genetic regulation.
