Search results for "Ribonucleotide"

Class 1 Histone Deacetylases and Ataxia-Telangiectasia Mutated Kinase Control the Survival of Murine Pancreatic Cancer Cells upon dNTP Depletion

2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with a dismal prognosis. Here, we show how an inhibition of de novo dNTP synthesis by the ribonucleotide reductase (RNR) inhibitor hydroxyurea and an inhibition of epigenetic modifiers of the histone deacetylase (HDAC) family affect short-term cultured primary murine PDAC cells. We used clinically relevant doses of hydroxyurea and the class 1 HDAC inhibitor entinostat. We analyzed the cells by flow cytometry and immunoblot. Regarding the induction of apoptosis and DNA replication stress, hydroxyurea and the novel RNR inhibitor COH29 are superior to the topoisomerase-1 inhibitor irinotecan which is used to treat PDAC. Ent…

A rapid separation of the four major deoxynucleosides and deoxyinosine by high-pressure liquid cation-exchange chromatography

1973

From the covalent linkage of drugs to novel inhibitors of ribonucleotide reductase: synthesis and biological evaluation of valproic esters of 3'-C-me…

2014

We synthesized a series of serum-stable covalently linked drugs derived from 3'-C-methyladenosine (3'-Me-Ado) and valproic acid (VPA), which are ribonucleotide reductase (RR) and histone deacetylase (HDAC) inhibitors, respectively. While the combination of free VPA and 3'-Me-Ado resulted in a clear synergistic apoptotic effect, the conjugates had lost their HDAC inhibitory effect as well as the corresponding apoptotic activity. Two of the analogs, 2',5'-bis-O-valproyl-3'-C-methyladenosine (A160) and 5'-O-valproyl-3'-C-methyladenosine (A167), showed promising cytotoxic activities against human hematological and solid cancer cell lines. A167 was less potent than A160 but had interesting featu…

An isocratic high-pressure liquid chromatographic purification method for radioactively labeled deoxyribonucleoside triphosphates.

1976

Abstract A method is described for the rapid purification of radioactively labeled deoxyribonucleoside tri­phosphates from their spontaneously emerging hydrolysis products deoxyribonucleoside diphosphate, deoxyribonucleoside monophosphate, and deoxyribonucleoside. The separations which are finished within 3 min or less are carried out on a 0.1X5 cm column filled with LiChrosorb-NH2 , using isocratic elution with 0.025 м potassium phosphate, pH 6 .8 , in a high-pressure liquid chromatograph at room temperature and a flow rate of 30 ml · h-1(flow velocity 63.7 cm·min-1).

Pharmacokinetics of oligodeoxynucleotides encapsulated in liposomes: effect of lipid composition and preparation method

2000

1. The effect of the method employed to prepare liposomes and their lipid composition were evaluated in terms of the encapsulation efficiency and pharmacokinetic features of two oligodeoxynucleotides of a 21 mer: the normal (N-Odn) and the phosphorothioate (S-Odn) oligodeoxynucleotide. 2. Liposomes were prepared by the classical method of multilamellar vesicles (MV) and by the dehydration-rehydration method (DR). Two lipid mixtures were used to prepare liposomes--the predominant lipid being phosphatidylcholine (PC) and sphingomyelin (SM) respectively. 3. The DR method for liposome preparation provided the highest encapsulation efficiency, regardless of liposome lipid composition and the typ…

Endoribonuclease IV. A poly(A)-specific ribonuclease from chick oviduct. 1. Purification of the enzyme.

1976

A new endoribonuclease, termed endoribonuclease IV, has been described. This enzyme has been isolated from chick oviducts and purified 15 000-fold in a 25% yield nearly to homogeneity. The nuclease, which specifically degrades poly(A), forms oligonucleotides of an average chain length of 10. These (A)-10 fragments are terminated by 3'-hydroxyl and 5'-phosphate groups. The enzyme has a pH optimum at 8.7, requires Mn2+ or Mg2+ as a cofactor, and has a molecular weight of about 45 000.

2′,5′-oligoadenylate synthetase from a lower invertebrate, the marine sponge Geodia cydonium, does not need dsRNA for its enzymatic activity

2002

AbstractRecently, the presence of 2′,5′-linked oligoadenylates and a high 2′,5′-oligoadenylate synthetase activity were discovered in a lower invertebrate, the marine sponge Geodia cydonium. It has been demonstrated that mammalian 2–5A synthetase isozymes require a dsRNA cofactor for their enzymatic activity. Our results show that, unlike mammalian 2–5A synthetases, the 2–5A synthetase from the sponge acts in a dsRNA-independent manner in vitro. A prolonged incubation of the G. cydonium extract with a high concentration of a micrococcal nuclease had no effect on the activity of the 2–5A synthetase. At the same time, the micrococcal nuclease was effective within 30 min in degrading dsRNA nee…

Molecular and physiological consequences of faulty eukaryotic ribonucleotide excision repair

2019

Abstract The duplication of the eukaryotic genome is an intricate process that has to be tightly safe‐guarded. One of the most frequently occurring errors during DNA synthesis is the mis‐insertion of a ribonucleotide instead of a deoxyribonucleotide. Ribonucleotide excision repair (RER) is initiated by RNase H2 and results in error‐free removal of such mis‐incorporated ribonucleotides. If left unrepaired, DNA‐embedded ribonucleotides result in a variety of alterations within chromosomal DNA, which ultimately lead to genome instability. Here, we review how genomic ribonucleotides lead to chromosomal aberrations and discuss how the tight regulation of RER timing may be important for preventin…

Neuronal Cell Nuclear Factor. A Nuclear Receptor Possibly Involved in the Control of Neurogenesis and Neuronal Differentiation

1997

We have cloned from a cDNA library of neuronal derivatives of retinoic-acid-induced embryonic carcinoma cells a nuclear receptor that may be involved in the control of late neurogenesis and early neuronal differentiation. The receptor which is practically identical in sequence with germ cell nuclear factor, has been designated neuronal cell nuclear factor (NCNF). NCNF is exclusively expressed in the neuronal derivatives of PCC7-Mz1 cells, with the expression beginning within hours of exposure to retinoic acid. In the developing mouse brain, NCNF is expressed in the marginal zones of the neuroepithelium which are known to contain young postmitotic neurons. NCNF binds to the DRO sequence ther…

Role for calnexin and N-linked glycosylation in the assembly and secretion of hepatitis B virus middle envelope protein particles.

1998

ABSTRACT Unlike those of the S and the L envelope proteins, the functional role of the related M protein in the life cycle of the hepatitis B virus (HBV) is less understood. We now demonstrate that a single N glycan, specific for M, is required for efficient secretion of M empty envelope particles. Moreover, this glycan mediates specific association of M with the chaperone calnexin. Conversely, the N glycan, common to all three envelope proteins, is involved neither in calnexin binding nor in subviral particle release. As proper folding and trafficking of M need the assistance of the chaperone, the glycan-dependent association of M with calnexin may thus play a crucial role in the assembly …