71295-94-8

Upstream product

• 182005-90-9 uridylyl (3'-5') 5'-amino-5'-deoxyuridine 
• 39483-48-2 5'-azido-5'-deoxyuridine 
• 362-43-6 2',3'-O-isopropylideneuridine 
• 7354-93-0 2',3'-O-isopropylidene-5'-O-tosyluridine 
• 15083-05-3 5'-azido-5'-deoxy-2',3'-O-isopropylideneuridine 
• 58-96-8 uridine 
• 68707-83-5 2',3'-O-p-methoxybenzylidene-5'-oxo-5'-deoxyuridine 
• 28370-56-1 5'-deoxy-5'-uridylaldehyde 
• 53166-52-2 2',3'-O-p-methoxybenzylideneuridine 
• 27999-65-1 (3aS,4S,6R,6aR)-6-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carbaldehyde 
• 58-97-9 5'-Uridylic Acid 

Downstream Products

• 1221257-00-6 C₂₆H₃₄N₄O₁₀ 
• 1330004-26-6 5-amino-5-deoxy-α-D-ribose 1-phosphate 
• 66-22-8 uracil 
• 63-37-6 cytidine monophosphate 
• 365-07-1 thymidine 5'-phosphate 
• 1330004-15-3 5-amino-5-deoxy-α-D-ribose-1,2-cyclic phosphate 
• 58-97-9 5'-Uridylic Acid 
• 58-98-0 UDP 
• 302917-20-0 5'-O-(5''-amino-5''-deoxy-β-D-ribosyl)uridine 
• 1330004-30-2 C₁₅H₁₈NO₇PS 
• 85-32-5 Guanosine 5'-monophosphate 
• 1338344-30-1 C₁₉H₂₃N₃O₉ 
• 1338344-26-5 C₁₆H₁₇N₃O₆ 
• 1338344-35-6 C₁₇H₁₉N₃O₇ 

Relevant academic research and scientific papers

Enzymatic Synthesis of the Ribosylated Glycyl-Uridine Disaccharide Core of Peptidyl Nucleoside Antibiotics

Muraymycins belong to a family of nucleoside antibiotics that have a distinctive disaccharide core consisting of 5-amino-5-deoxyribofuranose (ADR) attached to 6′-N-alkyl-5′-C-glycyluridine (GlyU). Here, we functionally assign and characterize six enzymes from the muraymycin biosynthetic pathway involved in the core assembly that starts from uridine monophosphate (UMP). The biosynthesis is initiated by Mur16, a nonheme Fe(II)- and α-ketoglutarate-dependent dioxygenase, followed by four transferase enzymes: Mur17, a pyridoxal-5′-phosphate (PLP)-dependent transaldolase; Mur20, an aminotransferase; Mur26, a pyrimidine phosphorylase; and Mur18, a nucleotidylyltransferase. The pathway culminates in glycosidic bond formation in a reaction catalyzed by an additional transferase enzyme, Mur19, a ribosyltransferase. Analysis of the biochemical properties revealed several noteworthy discoveries including that (i) Mur16 and downstream enzymes can also process 2′-deoxy-UMP to generate a 2-deoxy-ADR, which is consistent with the structure of some muraymycin congeners; (ii) Mur20 prefers l-Tyr as the amino donor source; (iii) Mur18 activity absolutely depends on the amine functionality of the ADR precursor consistent with the nucleotidyltransfer reaction occurring after the Mur20-catalyzed aminotransfer reaction; and (iv) the bona fide sugar acceptor for Mur19 is (5′S,6′S)-GlyU, suggesting that ribosyltransfer occurs prior to N-alkylation of GlyU. Finally, a one-pot, six-enzyme reaction was utilized to generate the ADR-GlyU disaccharide core starting from UMP.

Biosynthesis of the structurally unique polycyclopropanated polyketide-nucleoside hybrid jawsamycin (FR-900848)

The biosynthetic gene cluster of antifungal agent jawsamycin (FR-900848) has been identified by heterologous expression. A series of gene inactivations and in vitro and in vivo analysis of key enzymes in the biosynthetic pathway established their functions. A novel mechanism involving a radical S-adenosyl methionine (SAM) cyclopropanase collaborating with an iterative polyketide synthase is proposed for the construction of the unique polycyclopropanated backbone. Our reconstitution system sets the stage for studying the catalytic mechanism of this intriguing contiguous cyclopropanation. Jaws of life: The biosynthetic gene cluster of antifungal agent jawsamycin (FR-900848) has been identified by heterologous expression. A series of gene inactivations and in vitro and in vivo analysis of the key enzymes established their functions. A novel iterative polyketide synthase is proposed to collaborate with a trans-acting ketoreductase and a radical SAM cyclopropanase in constructing the unique polycyclopropanated backbone.

A DTTA-ligated uridine-quantum dot conjugate as a bimodal contrast agent for cellular imaging

A uridine-quantum dot conjugate, a contrast agent for multimodal imaging, was synthesized. Its T1 relaxivity was 655 and 571.2 mM-1 s-1 per particle at 36 °C in phosphate buffered saline at 60 and 200 MHz, respectively. In vitro multimodal images confirmed its uptake by RAW 264.7 cells. The Royal Society of Chemistry 2012.

Biogenesis of the unique 4′,5′-dehydronucleoside of the uridyl peptide antibiotic pacidamycin

The pacidamycins belong to a class of antimicrobial nucleoside antibiotics that act by inhibiting the clinically unexploited target translocase I, a key enzyme in peptidoglycan assembly. As with other nucleoside antibiotics, the pacidamycin 4′,5′-dehydronucleoside portion is an essential pharmacophore. Here we show that the biosynthesis of the pacidamycin nucleoside in Streptomyces coeruleorubidus proceeds through three steps from uridine. The transformations involve oxidation of the 5′-alcohol by Pac11, transamination of the resulting aldehyde by Pac5, and dehydration by the Cupin-domain protein Pac13.

Biosynthetic origin and mechanism of formation of the aminoribosyl moiety of peptidyl nucleoside antibiotics

Several peptidyl nucleoside antibiotics that inhibit bacterial translocase I involved in peptidoglycan cell wall biosynthesis contain an aminoribosyl moiety, an unusual sugar appendage in natural products. We present here the delineation of the biosynthetic pathway for this moiety upon in vitro characterization of four enzymes (LipM-P) that are functionally assigned as (i) LipO, an l-methionine:uridine-5′-aldehyde aminotransferase; (ii) LipP, a 5′-amino-5′-deoxyuridine phosphorylase; (iii) LipM, a UTP:5-amino-5-deoxy-α-d-ribose-1-phosphate uridylyltransferase; and (iv) LipN, a 5-amino-5-deoxyribosyltransferase. The cumulative results reveal a unique ribosylation pathway that is highlighted by, among other features, uridine-5′-monophosphate as the source of the sugar, a phosphorylase strategy to generate a sugar-1-phosphate, and a primary amine-requiring nucleotidylyltransferase that generates the NDP-sugar donor.

Nine enzymes are required for assembly of the pacidamycin group of peptidyl nucleoside antibiotics

Pacidamycins are a family of uridyl peptide antibiotics that inhibit the translocase MraY, an essential enzyme in bacterial cell wall biosynthesis that to date has not been clinically targeted. The pacidamycin structural skeleton contains a doubly inverted peptidyl chain with a β-peptide and a ureido linkage as well as a 3′-deoxyuridine nucleoside attached to DABA 3 of the peptidyl chain via an enamide linkage. Although the biosynthetic gene cluster for pacidamycins was identified recently, the assembly line of this group of peptidyl nucleoside antibiotics remained poorly understood because of the highly dissociated nature of the encoded nonribosomal peptide synthetase (NRPS) domains and modules. This work has identified a minimum set of enzymes needed for generation of the pacidamycin scaffold from amino acid and nucleoside monomers, highlighting a freestanding thiolation (T) domain (PacH) as a key carrier component in the peptidyl chain assembly as well as a freestanding condensation (C) domain (PacI) catalyzing the release of the assembled peptide by a nucleoside moiety. On the basis of the substrate promiscuity of this enzymatic assembly line, several pacidamycin analogues were produced using in vitro total biosynthesis.

Synthesis and biological activities of novel s-triazine bridged dinucleoside analogs

A series of novel dinucleosides linked by s-triazine were synthesized via the nucleophilic substitution reaction of amino nucleoside and cyanuric chloride in THF/H2O. The biological activities of these novel dinucleoside analogs against HIV-RT, HeLa and A-549 cell lines in vitro were evaluated. Copyright

Synthesis and properties of RNA analogues having amides as interuridine linkages at selected positions

Oligoribonucleotide analogues having amide internucleoside linkages (AM1: 3′-CH2CONH-5′ and AM2: 3′-CH 2NHCO-5′) at selected positions have been synthesized and the thermal stability of duplexes formed by these analogues with complem

Nucleoside derivatives

Novel nucleoside derivatives represented by the following general formula (1): 1wherein X is(are) the same or different and each represents a pyrimidine or purine base or a derivative thereof, Y-and Y′ are the same or different and each represents at least one amino acid or amino acid derivative selected from the group consisting of serine, threonine, ornithine, aspartic acid, glutamic acid, lysine, arginine, cysteine, methionine, δ-hydroxylysine, N-aminoethylglycine, N-aminoethylserine, N-aminoethyllysine, N-aminoethylornithine, N-aminoethylaspartic acid, N-aminoethylglutamic acid, homoglutamic acid, β-thiocarbonylaspartic acid, γ-thiocarbonylglutamic acid, and δ-thiocarbonylhomoglutamic acid, R1 represents a hydrogen atom or a hydroxyl group, A represents a single bond or a carbonyl or thiocarbonyl group, 1 is an integer of 0 to 5, and n is an integer of 1 to 100.

Synthesis and properties of diuridine phosphate analogues containing thio and amino modifications

Several analogues of diuridine phosphate (UpU) were synthesized in order to investigate why replacing the 2'-hydroxyl with a 2'-amino group prevents hydrolysis. These analogues were designed to investigate what influence the 2'-substituent and 5'-leaving group have upon the rate of hydrolysis. All the analogues were considerably more labile than UpU toward acid-base-catalyzed hydrolysis. In the pH region from 6 to 9, the rate of hydrolysis of uridylyl (3'-5') 5'-thio-5'deoxyuridine (UpsU) hydrolysis rose, in a log linear fashion, from a value of 5 x 10-6 s-1 at pH 6 to 3200 x 10-6 s-1 at pH 9, indicating that attack on the phosphorus by the 2'-oxo anion is rate-limiting in the hydrolysis mechanism. In contrast, the rate of uridylyl (3'-5') 5'-amino-5'deoxyuridine (UpnU) hydrolysis fell from a value of 1802 x 10-6 s-1 at pH 5 to 140 x 10-6 s-1 at pH 7.5, where it remained constant up to pH 11.5, thus indicating an acid-catalyzed reaction. The analogue 2'-amino-2'-deoxyuridylyl (3'-5') 5'-thio-5'-deoxyuridine (amUpsU) was readily hydrolyzed above pH 7, in contrast to the hydrolytic stability of amUpT, with rates between 85 x 10-6 s-1 and 138 x 10-6 s-1. The hydrolysis of 2'-amino-2'-deoxyuridylyl (3'-5') 5'-amino-5'-deoxythymidine (amUpnT) rose from 17 x 10-6 s-1 at pH 11.5 to 11 685 x 10-6 s-1 at pH 7.0, indicating an acid-catalyzed reaction, where protonation of the 5'-amine is rate limiting. The cleavage rates of UpsU, UpnU, and amUpsU were accelerated in the presence of Mg2+,Zn2+, and Cd2+ ions, but a correlation with interaction between metal ion and leaving group could only be demonstrated for amUpsU. UpsU and UpnU are also substrates for RNase A with UpsU having similar Michaelis-Menten parameters to UpU. In contrast, UpnU is more rapidly degraded with an approximate 35-fold increase in catalytic efficiency, which is reflected purely in an increase in the value of κ(cat).