Amido phosphoribosyltransferase (APRT) catalyzes the first step of the de novo biosynthesis of purine nucleotides, the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) into 5-phosphoribosylamine (PRA). APRT is a valid target for development of inhibitors as anticancer drugs. We have develop...
We evaluated inosine monophosphate dehydrogenase (IMPDH) 1 and IMPDH2 pharmacogenetics in 247 recipient–donor pairs after nonmyeloablative hematopoietic cell transplant (HCT). Patients were conditioned with total body irradiation + fludarabine and received grafts from related or unrelated donor...
The rate of decomposition of aqueous solutions of 5-phosphoribosyl-α-1-pyrophosphate (PRPP) is greatly enhanced by the presence of certain divalent ions. High levels of Mg2+ were shown to increase the rate of phosphate removal from PRPP by factors greater than 100-fold. The combined action of M...
Nowadays enzymatic synthesis of nucleic acid derivatives is gaining momentum over traditional chemical synthetic processes. Biotransformations catalyzed by whole cells or enzymes offer an ecofriendly and efficient alternative to the traditional multistep chemical methods, avoiding the use of che...
Several carbocyclic phosphonate analogs of 2′,3′-dideoxyadenosine-5′-monophosphate (ddAMP) were pyrophosphorylated by E. coli 5-phosphoribosyl-1-pyrophosphate (PRPP) synthetase in the presence of PRPP. Structure-activity relationships are discussed.
Multivariate curve resolution is proposed for the analysis of spectroscopic data obtained from kinetic studies on the interaction of compounds analogous to cis-platinum (cisplatin) and nucleic acids. In particular, the interaction between the cis-dichloro-(1,2-diethyl-3-aminopyrrolidine) Pt(II) ...
3′Cytidylic acid was irradiated with ultraviolet light to produce as the main photoproduct C*p.† The absorption spectrum of C*p has maxima at 240 and 210 mμ and has a pK of 5·56. It was separated from Cp by rapid high-voltage electrophoresis (20 minutes 0°C at pH 4·4). The separated C*p was...
1. Cytidine 2′(3′)-phosphate can be condensed in the presence of polyphosphoric acid.2. The product was found to contain polyphosphate end groups which, however, could be removed by treatment with Escherichia coli alkaline phosphatase (EC 3.1.3.1).3. A single 2′(3′)-P-terminal end group was ...
An efficient route to 2′-homouridine (1), a new nucleoside analogue, is reported that is based on an ene reaction. This nucleoside has been incorporated into a dinucleoside monophosphate and hydrolytic studies on the dimer show that it does not behave like a ribonucleotide.
In recent years, orotidine-5′-monophosphate decarboxylase (ODCase) has gained renewed attention as a drug target. As a part of continuing efforts to design novel inhibitors of ODCase, we undertook a comprehensive study of potent, structurally diverse ligands of ODCase and analyzed their structu...
Salinity is one of the major abiotic stresses that limits agricultural productivity worldwide. Plant roots function as the primary site of salinity perception. Salt responses in roots are essential for maintaining root functionality, as well as for transmitting the salt signal to shoot for prope...
Novel ribonucleoside 3′,5′-cyclic monophosphorodithioates were synthesized by a combination of the phosphoramidite and phosphotriester methods. These include uridine 3′,5′-cyclic monophosphorodithioate (cUMPS2), cytidine 3′,5′-cyclic monophosphorodithioate (cCMPS2), and guanosine 3′,5′-c...
Fluorine is an essential trace element to which humans and animals are exposed through water, food, air and products used for dental health. Numerous studies have reported the detrimental effects of fluoride on testicular function and fertility; however, the underlying mechanisms of testosterone...
Our aim was to explore the preventive and therapeutic effects of sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate (brand name: brozopine, BZP) on stroke in Dahl Salt-sensitive (Dahl-SS) hypertensive rats. Dahl-SS rats were fed a high-salt diet to observe the effect of BZP on blood pressure, and...
Corin is a protease that activates atrial natriuretic peptide, a cardiac hormone important in the control of blood pressure and salt–water balance. Here we examined the role of corin in regulating blood pressure and sodium homeostasis upon dietary salt challenge. Radiotelemetry-tracked blood pr...
Blood pressure salt sensitivity and salt resistance are mechanistically imperfectly explained. A prescient systems medicine approach by Guyton and colleagues—more than 50 years ago—suggested how salt intake might influence blood pressure. They proposed that a high-salt diet engenders sodium ac...
Cyclic guanosine monophosphate (cGMP) is an important second messenger molecule involved in gating ion channels and activating protein kinases. Here, we describe a validated LC–MS/MS method for the quantification of cGMP in human plasma, utilizing a stable isotope labeled analogue of cGMP as I....
Reactive nitrogen species (RNS) have gained a significant attention in recent years due to their indispensable role in mechanisms regulating various biological processes of plant growth and development under normal as well as in stress conditions. RNS, including nitric oxide, nitrogen dioxide, n...
A robust high-performance liquid chromatography tandem mass spectrometry (LC–MS/MS) assay was developed and qualified for the measurement of cyclic nucleotides (cNTs) in rat brain tissue. Stable isotopically labeled 3′,5′-cyclic adenosine-13C5 monophosphate (13C5-cAMP) and 3′,5′-cyclic guan...
Sildenafil and tadalafil are widely-used phosphodiesterase 5 (PDE5) inhibitors for which no clear dose-response relationship could be established. Using isolated and/or recombinant PDE5, it has been demonstrated that cGMP can increase the affinity of this enzyme for sildenafil and tadalafil. We ...
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