Chemical and Metabolic Properties of Adenosine Diphosphate Ribose Derivatives of Nuclear Proteins

1974 ◽  
Vol 2 (1) ◽  
pp. 95-96
Author(s):  
J. A. SMITH ◽  
L. A. STOCKEN
Keyword(s):  
Adenosine Diphosphate ◽  
Nuclear Proteins ◽  
Metabolic Properties ◽  
Derivatives Of

scholarly journals Chemical and metabolic properties of adenosine diphosphate ribose derivatives of nuclear proteins.

1975 ◽  
Vol 147 (3) ◽  
pp. 523-529 ◽  
Author(s):  
J A Smith ◽  
L A Stocken
Keyword(s):  
Adenosine Diphosphate ◽  
S Phase ◽  
The Other ◽  
Hydroxyl Group ◽  
Small Peptide ◽  
Histone 3 ◽  
Liver Nuclei ◽  
Metabolic Properties ◽  
Derivatives Of ◽  
Covalently Bound

1. ADP-ribose is found in rat liver nuclei covalently bound to histone F1, to a non-histone protein, and to a small peptide. 2. A single unit of ADP-ribose, covalently bound to phosphoserine, was isolated from an enzymic hydrolysate of histone F1. ADP-ribose-bearing peptides were isolated from a tryptic digest of the histone. 3. It is proposed that the 1′-hydroxyl group of ADP-ribose is linked to the phosphate group of phosphoserine in histone F1. 4. The incorporation of 32P into ADP-ribose on histone F1 a parallels the DNA content through the cell cycle. An increased incorporation of the nucleotide into the other derivatives is observed during S phase. 5. It is suggested that the ADP-ribose derivative of histone F1 has a role in maintaining the G0 state and that one or both of the other derivatives is concerned with control of DNA synthesis.

Assessment of the Physicochemical Properties and Stability for Pharmacokinetic Prediction of Pyrazinoic Acid Derivatives

2020 ◽  
Vol 21 (9) ◽  
pp. 714-721
Author(s):  
Taísa Busaranho Franchin ◽  
Bruna Cristina Ulian Silva ◽  
Rone Aparecido DeGrandis ◽  
Michelle Fidelis Corrêa ◽  
Cecília Maria Simões de Queiroz Aranha ◽  
...  
Keyword(s):  
Antimycobacterial Activity ◽  
Pharmacokinetic Profile ◽  
Rat Plasma ◽  
Apparent Permeability ◽  
High Prevalence ◽  
Metabolic Properties ◽  
The Stability ◽  
Derivatives Of ◽  
Acid Esters ◽  
Pyrazinoic Acid

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, which still has high prevalence worldwide. In addition, cases of drug resistance are frequently observed. In the search for new anti-TB drugs, compounds with antimycobacterial activity have been developed, such as derivatives of pyrazinoic acid, which is the main pyrazinamide metabolite. In a previous study, the compounds were evaluated and showed moderate antimycobacterial activity and no important cytotoxic profile; however, information about their pharmacokinetic profile is lacking. Objective: The aim of this work was to perform physicochemical, permeability, and metabolic properties of four pyrazinoic acid esters. Methods: The compounds were analyzed for their chemical stability, n-octanol:water partition coefficient (logP) and apparent permeability (Papp) in monolayer of Caco-2 cells. The stability of the compounds in rat and human microsomes and in rat plasma was also evaluated. Results: The compounds I, II and IV were found to be hydrophilic, while compound III was the most lipophilic (logP 1.59) compound. All compounds showed stability at the three evaluated pHs (1.2, 7.4 and 8.8). The apparent permeability measured suggests good intestinal absorption of the compounds. Additionally, the compounds showed metabolic stability under action of human and rat microsomal enzymes and stability in rat plasma for at least 6 hours. Conclusion: The results bring favorable perspectives for the future development of the evaluated compounds and other pyrazinoic acid derivatives.

scholarly journals Clotting activity of camphene derivatives

2015 ◽  
Vol 96 (3) ◽  
pp. 455-458 ◽  
Author(s):  
A A Rakhmatullina ◽  
R G Turaev ◽  
S V Kiselev ◽  
L E Nikitina ◽  
A V Bodrov
Keyword(s):  
Anticoagulant Activity ◽  
Catalyst Activity ◽  
Venous Blood ◽  
Adenosine Diphosphate ◽  
Human Blood Plasma ◽  
Clotting Factors ◽  
13C Nuclear Magnetic Resonance ◽  
Derivatives Of ◽  
Sulfur Containing

Aim. To study of the influence of new synthetized sulfur-containing derivatives of camphene on the thrombocytes aggregating ability and clotting activity of human blood plasma in vitro. Methods. Sulfides and sulphones of camphene were synthesized by thiols electrophilic addition reaction. The structures of the synthetized compounds were clarified by using of 1H and 13C nuclear magnetic resonance, chromato-mass spectrometry and X-ray analysis. Clotting activity of the synthetized compounds was assessed by studying the spontaneous platelet aggregation and plasma coagulating activity of the venous blood of patients with ischemic heart disease. The induced platelets aggregation was studied on plasma obtained from healthy donors. Results. The synthetized compounds demonstrated anti-aggregating and anti-coagulating activity: they inhibited spontaneous and induced thrombocyte aggregation as well as reduced coagulating ability of human plasma. Both camphene sulphone and mainly camphene sulfide (in contrast with acetylsalicylic acid and clopidogrel) totally inhibited thrombocytes aggregation induced by adrenaline, adenosine diphosphate, collagen and arachidonic acid, and decreased the influence of ristocetin. Anticoagulant activity of the synthetized substances is associated to their potential to inhibit thrombocyte activation and to reduce the catalyst activity of phospholipid surface participating in coagulating complexes and clotting factors formation. Conclusion. Low toxicity of terpenoids together with discovered anticoagulant activity of sulfur-containing derivatives of camphene revealing the promising potential of these drugs for further development of novel medical treatments for treating and prevention of different types of thrombophilia.

The Effect of Intravenous Adenosine Diphosphate on the Number of Circulating Platelets in Experimental Animals: Inhibition by Prostaglandin E1, Dipyridamole, SH-869 and VK-774

1977 ◽  
Vol 37 (01) ◽  
pp. 036-046 ◽  
Author(s):  
Ian B. Holmes ◽  
Gordon M. Smith ◽  
Franz Freuler
Keyword(s):  
Prostaglandin E1 ◽  
Potent Inhibitor ◽  
Adenosine Diphosphate ◽  
Dependent Manner ◽  
Response Curves ◽  
Duration Of Action ◽  
Intravenous Infusions ◽  
Long Duration ◽  
Dose Dependent ◽  
Derivatives Of

SummaryThe number of circulating platelets was monitored in anaesthetized animals by a continuous flow technique, using a Technicon Autocounter®. Intravenous infusions of adenosine diphosphate (ADP) produced transient, dose-dependent falls in circulating platelet numbers in rabbits, dogs, rats, pigs and squirrel monkeys. The rat was the most sensitive of the species investigated.In the rabbit, the effect of a submaximal dose of ADP was inhibited in a dose-dependent manner by intravenous infusions of prostaglandin E1 (PGE1), dipyridamole, and two derivatives of dipyridamole (SH-869 and VK-774). The dose-response curves for PGEl, SH-869 and VK-774 were approximately parallel, whereas that for dipyridamole was considerably less steep. PGE1 was the most potent inhibitor, but the duration of action was very short. Dipyridamole and SH-869 produced inhibition of long duration. The duration of action of VK-774 was intermediate.All inhibitors produced marked and often long-lasting hypotension. The fact that no inhibition of ADP effects could be demonstrated with dibenzyline and hexamethonium, which also produced marked hypotension of long duration, indicated that inhibition of the ADP effect by the four antagonists studied was not due to changes in blood pressure.

scholarly journals Poly(adenosine diphosphate ribose) synthetase activity in nuclei of dividing and of non-dividing but differentiating intestinal epithelial cells

1979 ◽  
Vol 180 (3) ◽  
pp. 455-461 ◽  
Author(s):  
J W Porteous ◽  
H M Furneaux ◽  
C K Pearson ◽  
C M Lake ◽  
A Morrison
Keyword(s):  
Small Intestine ◽  
Epithelial Cells ◽  
Guinea Pig ◽  
Intestinal Epithelial Cells ◽  
Adenosine Diphosphate ◽  
Crypt Cell ◽  
Nuclear Proteins ◽  
Synthetase Activity ◽  
Intestinal Epithelial ◽  
Cell Nuclei

Poly(ADP-ribose) synthetase activity is found in nuclei of regenerating epithelial cells in the lower half of the crypts of guinea-pig small intestine. Nuclei from non-dividing but differentiating and maturing cells in the upper crypts and on the villi contain no more than about 10% of the synthetase activity of lower-crypt cell nuclei. The product in the active nuclei is shown to be 80% poly(ADP-ribosylated) protein and 20% mono(ADP-ribosylated) protein; 60% of thetotal labelled product was attached to acid-soluble proteins (including histones), and 40% to acid-insoluble (non-histone) proteins. The average number of ADP-ribosyl units in the oligomeric chains of the poly(ADP-ribosylated) proteins was 15 but the range of sizes of (ADP-ribose) oligomers attached to nuclear proteins was smaller in villus than in crypt cell nuclei.

Protamine-DNA interaction

1978 ◽  
Vol 36 (2) ◽  
pp. 200-201
Author(s):  
D.P. Bazett-Jones ◽  
F.P. Ottensmeyer
Keyword(s):  
Small Volume ◽  
Double Helix ◽  
Dna Interaction ◽  
Dark Field ◽  
Sperm Head ◽  
Nuclear Proteins ◽  
Field Electron Microscopy ◽  
Dark Field Electron ◽  
Dna Double Helix ◽  
Positively Charged

Dark field electron microscopy has been used for the study of the structure of individual macromolecules with a resolution to at least the 5Å level. The use of this technique has been extended to the investigation of structure of interacting molecules, particularly the interaction between DNA and fish protamine, a class of basic nuclear proteins of molecular weight 4,000 daltons.Protamine, which is synthesized during spermatogenesis, binds to chromatin, displaces the somatic histones and wraps up the DNA to fit into the small volume of the sperm head. It has been proposed that protamine, existing as an extended polypeptide, winds around the minor groove of the DNA double helix, with protamine's positively-charged arginines lining up with the negatively-charged phosphates of DNA. However, viewing protamine as an extended protein is inconsistent with the results obtained in our laboratory.

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