scholarly journals Pharmacokinetic properties of a novel formulation of S-adenosyl-l-methionine phytate

Amino Acids ◽  
2021 ◽  
Author(s):  
Antonio Francioso ◽  
Sergio Fanelli ◽  
Maria d’Erme ◽  
Eugenio Lendaro ◽  
Niccolò Miraglia ◽  
...  
Keyword(s):  
Amino Acid ◽  
Steric Hindrance ◽  
Cellular Metabolism ◽  
Food Supplement ◽  
Pharmacokinetic Parameters ◽  
Pharmacological Properties ◽  
Methyl Donor ◽  
Pharmacokinetic Properties ◽  
Amino Acid Methionine ◽  
New Form

AbstractS-adenosyl-l-methionine (SAM), the main endogenous methyl donor, is the adenosyl derivative of the amino acid methionine, which displays many important roles in cellular metabolism. It is widely used as a food supplement and in some countries is also marketed as a drug. Its interesting nutraceutical and pharmacological properties prompted us to evaluate the pharmacokinetics of a new form of SAM, the phytate salt. The product was administered orally to rats and pharmacokinetic parameters were evaluated by comparing the results with that obtained by administering the SAM tosylated form (SAM PTS). It was found that phytate anion protects SAM from degradation, probably because of steric hindrance exerted by the counterion, and that the SAM phytate displayed significant better pharmacokinetic parameters compared to SAM PTS. These results open to the perspective of the use of new salts of SAM endowed with better pharmacokinetic properties.

scholarly journals Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes

2016 ◽  
Vol 113 (8) ◽  
pp. 2104-2109 ◽  
Author(s):  
Ben Murray ◽  
Svetlana V. Antonyuk ◽  
Alberto Marina ◽  
Shelly C. Lu ◽  
Jose M. Mato ◽  
...  
Keyword(s):  
Amino Acid ◽  
Crystal Structures ◽  
Active Site ◽  
Catalytic Site ◽  
Methionine Adenosyltransferase ◽  
Atomic Resolution ◽  
Structural Elements ◽  
Methyl Donor ◽  
Colon Cancers ◽  
Amino Acid Methionine

The principal methyl donor of the cell, S-adenosylmethionine (SAMe), is produced by the highly conserved family of methionine adenosyltranferases (MATs) via an ATP-driven process. These enzymes play an important role in the preservation of life, and their dysregulation has been tightly linked to liver and colon cancers. We present crystal structures of human MATα2 containing various bound ligands, providing a “structural movie” of the catalytic steps. High- to atomic-resolution structures reveal the structural elements of the enzyme involved in utilization of the substrates methionine and adenosine and in formation of the product SAMe. MAT enzymes are also able to produce S-adenosylethionine (SAE) from substrate ethionine. Ethionine, an S-ethyl analog of the amino acid methionine, is known to induce steatosis and pancreatitis. We show that SAE occupies the active site in a manner similar to SAMe, confirming that ethionine also uses the same catalytic site to form the product SAE.

The staining pattern of the tropomyosin sequence is displayed in a new paracrystal

1986 ◽  
Vol 44 ◽  
pp. 150-151
Author(s):  
M.K. Lamvik ◽  
L.L. Klatt
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Staining Pattern ◽  
Banding Patterns ◽  
Mass Thickness ◽  
New Form

Tropomyosin paracrystals have been used extensively as test specimens and magnification standards due to their clear periodic banding patterns. The paracrystal type discovered by Ohtsuki1 has been of particular interest as a test of unstained specimens because of alternating bands that differ by 50% in mass thickness. While producing specimens of this type, we came across a new paracrystal form. Since this new form displays aligned tropomyosin molecules without the overlaps that are characteristic of the Ohtsuki-type paracrystal, it presents a staining pattern that corresponds to the amino acid sequence of the molecule.

Cationic Antimicrobial Peptides for Tuberculosis: A Mini-Review

2019 ◽  
Vol 20 (9) ◽  
pp. 885-892
Author(s):  
Sara Silva ◽  
Nuno Vale
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Amino Acid ◽  
Antimicrobial Peptides ◽  
Resistance Mechanisms ◽  
Therapeutic Agents ◽  
Pharmacological Properties ◽  
Therapeutic Activity ◽  
Alternative Strategies ◽  
Cationic Antimicrobial Peptides ◽  
Specific Amino Acid

Cationic antimicrobial peptides (CAMPs) can be considered as new potential therapeutic agents for Tuberculosis treatment with a specific amino acid sequence. New studies can be developed in the future to improve the pharmacological properties of CAMPs and also understand possible resistance mechanisms. This review discusses the principal properties of natural and/or synthetic CAMPs, and how these new peptides have a significant specificity for Mycobacterium tuberculosis. Also, we propose some alternative strategies to enhance the therapeutic activity of these CAMPs that include coadministration with nanoparticles and/or classic drugs.

scholarly journals Peptide drugs for photopharmacology: how much of a safety advantage can be gained by photocontrol?

2020 ◽  
Vol 2 (1) ◽  
pp. FDD28 ◽  
Author(s):  
Oleg Babii ◽  
Sergii Afonin ◽  
Tim Schober ◽  
Liudmyla V Garmanchuk ◽  
Liudmyla I Ostapchenko ◽  
...  
Keyword(s):  
Chemotherapeutic Agent ◽  
In Vitro Cytotoxicity ◽  
Pharmacokinetic Parameters ◽  
Cancer Model ◽  
Pharmacokinetic Properties ◽  
Insight Into ◽  
Safety Advantage ◽  
Murine Cancer Model

Aim: To verify whether photocontrol of biological activity could augment safety of a chemotherapeutic agent. Materials & methods: LD50 values for gramicidin S and photoisomeric forms of its photoswitchable diarylethene-containing analogs were determined using mice. The results were compared with data obtained from cell viability measurements taken for the same compounds. Absorption, Distribution, Metabolism, and Elimination (ADME) tests using a murine cancer model were conducted to get insight into the underlying reasons for the observed in vivo toxicity. Results: While in vitro cytotoxicity values of the photoisomers differed substantially, the differences in the observed LD50 values were less pronounced due to unfavorable pharmacokinetic parameters. Conclusion: Despite unfavorable pharmacokinetic properties as in the representative case studied here, there is an overall advantage to be gained in the safety profile of a chemotherapeutic agent via photocontrol. Nevertheless, optimization of the pharmacokinetic parameters of photoisomers is an important issue to be addressed during the development of photopharmacological drugs.

scholarly journals Evaluation of pharmacokinetic properties of isobornylphenols in silico

2020 ◽  
Vol 35 (4) ◽  
pp. 79-86
Author(s):  
O. I. Ostrikova ◽  
O. E. Vaizova ◽  
O. I. Aliev ◽  
E. V. Buravlev ◽  
I. Yu. Chukicheva ◽  
...  
Keyword(s):  
Toxicity Assessment ◽  
Pharmacokinetic Parameters ◽  
Structure Property ◽  
Solubility In Water ◽  
Virtual Tools ◽  
Internet Resources ◽  
P Glycoprotein ◽  
Pharmacokinetic Properties ◽  
Low Toxicity ◽  
Low Solubility

Introduction. The potential of a new compound in the ongoing drugs discovery process is initially explored using virtual instruments, where its activity is predicted based on its molecular structure.Aim. This study aimed to evaluate the pharmacokinetic parameters and possible toxicity of isobornyl compounds based on virtual tools.Material and Methods. Several free Internet resources were used to assess the absorption, distribution, metabolism, excretion (ADME), and toxicity (T) of 2,6-diisobornyl-4-methylphenol (1, Dibornol), 2-hydroxy-3-isobornyl-5-methylbenzaldehyde (2), and 2-((di-n-butylamino) methyl)-6-isobornyl-4-methylphenol (3). Pharmacokinetic properties were calculated on ADMETlab platform. Toxicity and physical properties were evaluated using TEST software based on the structure-property quantification models of organic substances according to structure–property principle. Web server ProTox_II was used for acute toxicity assessment.Results. Plasma protein binding degrees were 76,9% for (1), 85,9% for (2), and 91,8% for (3). All three compounds were capable of penetrating the blood-brain barrier. Dibornol was identified neither as a substrate nor as an inhibitor of P-glycoprotein unlike (2) and (3). The half-life of all compounds was short (about 2 hours); the clearance was slow (about 2 mL/min*kg). The study showed that (2) and (3) potentially exert the toxic effects during the developmental stage of the organism, while ADMETlab showed potential cardio- and hepatotoxicity for (2) and (3), respectively. All compounds had extremely low solubility in water, which affected the assessments of other indicators by TEST software. The ProTox_II server showed the extremely low toxicity LD50 for all compounds (toxicity class 5).

ChemInform Abstract: N-(INDOL-3-YLGLYOXYL) AMINO ACID DERIVATIVES. PREPARATION AND PHARMACOLOGICAL PROPERTIES

1985 ◽  
Vol 16 (20) ◽  
Author(s):  
A. DA SETTIMO ◽  
G. PRIMOFIORE ◽  
A. M. MARINI ◽  
I. TONETTI ◽  
P. L. FERRARINI ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Derivatives ◽  
Pharmacological Properties

Biogenic amino acid methionine-based corrosion inhibitors of mild steel in acidic media

2019 ◽  
Vol 26 (4) ◽  
pp. 467-482 ◽  
Author(s):  
L. K. M. O. Goni ◽  
M. A. Jafar Mazumder ◽  
S. A. Ali ◽  
M. K. Nazal ◽  
H. A. Al-Muallem
Keyword(s):  
Amino Acid ◽  
Mild Steel ◽  
Corrosion Inhibitors ◽  
Acidic Media ◽  
Amino Acid Methionine

OXYTOCIN AS A NEUROHYPOPHYSIAL HORMONE IN THE HOLOCEPHALIAN ELASMOBRANCH FISH, HYDROLAGUS COLLEI

1969 ◽  
Vol 45 (4) ◽  
pp. 597-606 ◽  
Author(s):  
B. T. PICKERING ◽  
H. HELLER
Keyword(s):  
Amino Acid ◽  
Pituitary Gland ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
The Other ◽  
Pharmacological Properties ◽  
Neurohypophysial Hormones ◽  
Elasmobranch Fish

SUMMARY Two peptides with uterotonic activity have been isolated from the pituitary gland of a holocephalian elasmobranch fish: Hydrolagus collei. One of them had an amino acid composition compatible with that of oxytocin itself, and also had the pharmacological properties of this hormone. The other peptide which was present in much smaller amounts was basic by chromatography and had the pharmacological characteristics of [8-arginine]-oxytocin. It was not completely purified because of the small amount available, but its amino acid composition was in accord with that of vasotocin. The implications of the presence of oxytocin in such a primitive fish on the phylogeny, and hence probably the evolution, of neurohypophysial hormones are discussed.

scholarly journals A First-in-Human Study To Assess the Safety and Pharmacokinetics of Monoclonal Antibodies against Human Cytomegalovirus in Healthy Volunteers

2016 ◽  
Vol 60 (5) ◽  
pp. 2881-2887 ◽  
Author(s):  
Kiran Dole ◽  
Florencia Pereyra Segal ◽  
Adam Feire ◽  
Baldur Magnusson ◽  
Juan C. Rondon ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Healthy Volunteers ◽  
Human Cytomegalovirus ◽  
Treatment Options ◽  
Human Study ◽  
Pharmacokinetic Parameters ◽  
Apparent Relationship ◽  
Pharmacokinetic Properties ◽  
Human Igg1 ◽  
The Individual

ABSTRACTHuman cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the function of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. Here, we evaluated the safety, tolerability, and pharmacokinetics of a single intravenous dose of LJP538 or LJP539 or their combination in healthy volunteers. Adverse events and laboratory abnormalities occurred sporadically with similar incidence between antibody and placebo groups and without any apparent relationship to dose. No subject who received antibody developed a hypersensitivity, infusion-related reaction or anti-drug antibodies. After intravenous administration, both LJP538 and LJP539 demonstrated typical human IgG1 pharmacokinetic properties, with slow clearances, limited volumes of distribution, and long terminal half-lives. The pharmacokinetic parameters were linear and dose proportional for both antibodies across the 50-fold range of doses evaluated in the study. There was no apparent impact on pharmacokinetics when the antibodies were administered alone or in combination. CSJ148 and the individual monoclonal antibodies were safe and well tolerated, with pharmacokinetics as expected for human immunoglobulin.

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