scholarly journals Synthesis and Crystalline Structure of Zinc Complexes with Antihypertensive Drug Lisinopril

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Márcia C. de Souza ◽  
Luan F. Diniz ◽  
Chris H. J. Franco ◽  
Renata Diniz
Keyword(s):  
Structural Investigation ◽  
Zinc Complexes ◽  
One Dimensional ◽  
1D Coordination Polymer ◽  
Structural Differences ◽  
Synthetic Routes ◽  
Solvothermal Conditions ◽  
Formation Of Complexes

The structural investigation of Zn2+ complexes with the ligand lisinopril (LIS), an inhibitor of angiotensin-converting enzyme (ACE), was performed. The main objective is to compare if Zn-LIS coordination in vitro is similar to that observed in vivo. Two zinc complexes were obtained from different synthetic routes. The synthesis of LISZn1 used stirring, while for LISZn2 involved solvothermal conditions, which favoured the full deprotonation of lisinopril ligand. In this sense, the different synthetic routes resulted in the formation of complexes with notorious chemical and structural differences. The crystal structure of LISZn2 showed that the ligand is coordinated to Zn2+ ion by oxygen and nitrogen atoms which is different from that observed in vivo. In vitro, the coordination of lisinopril occurs only by an oxygen atom of the central carboxylate group. LISZn2 forms a one-dimensional (1D) coordination polymer and presents disorder atoms in its unit cell.

Chemistry of the phytochrome photoconversions

1983 ◽  
Vol 303 (1116) ◽  
pp. 377-386 ◽  
Keyword(s):  
Chemical Structure ◽  
Red Shift ◽  
Structural Differences

The photoconversions of phytochrome, P r ⇌ P fr , occur both in vivo and in vitro . Structural differences between P r and P fr are discussed for chromophore and apoprotein. The chemical structure of the P r chromophore has been established. The P fr chromophore was recently demonstrated to be the 15 E isomer. The red shift of absorption to 730 nm in native P fr is discussed as interaction between chromophore and apoprotein. The nature of this interaction is still unknown. Small changes in the apoprotein surface are of particular interest because they could be part of the signal chain in photoperception.

Yolk platelet degradation in preemergence Artemia embryos: response to protons in vivo and in vitro

1987 ◽  
Vol 252 (4) ◽  
pp. R774-R781 ◽  
Author(s):  
P. J. Utterback ◽  
S. C. Hand
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Dry Weight ◽  
Platelet Protein ◽  
Transmission Electron ◽  
Structural Differences ◽  
Alkaline Conditions ◽  
Yolk Platelet

Alteration of intracellular pH (pHi) influences yolk platelet degradation during preemergence development in Artemia embryos. Cysts incubated for 10 h under conditions of aerobic development (aqueous medium equilibrated with 60% N2-40% O2, pHi greater than or equal to 7.9) exhibit a significant decrease in numbers of yolk platelets and platelet protein. In contrast, cysts incubated for 10 h under aerobic acidosis (60% CO2-40% O2, pHi = 6.8) show no significant decrease in numbers of yolk platelets or platelet protein. When subjected to alkaline conditions in vitro, yolk platelets release protein exponentially as a function of time. The process is essentially complete in 40 min. The extent of protein and lipid release from platelets increases markedly as pH of the medium is raised in increments from 6.3 to 8.0. Concomitant with these changes are reduction (50%) in platelet dry weight and reduction (21%) in platelet diameter. Transmission electron microscopy does not reveal major structural differences between isolated yolk platelets and those contained in hydrated embryos. The proton effects on platelet composition and size detected in vitro may explain in part the mechanism of platelet degradation observed during aerobic development and its suppression under conditions of acidic pHi.

One Dimensional Experimental Setup to Study the Heating of Nanoparticle Laden Systems

2010 ◽  
Author(s):  
Zhenpeng Qin ◽  
John C. Bischof
Keyword(s):  
Small Volume ◽  
Laser Energy ◽  
Special Kind ◽  
Gold Nanoshells ◽  
Experimental Setup ◽  
Heat Absorption ◽  
One Dimensional ◽  
Lumped Models

Intensive efforts have been put into the use of gold nanoparticles (GNPs) for the enhancement of hyperthermia using laser in recent years since the groundbreaking work of Hirsh et al.(1) using gold nanoshells (GNS). Both in vitro (2), and in vivo (3) studies show promising results. For example, GNS, a special kind of GNP, are being manufactured and are in clinical trials (Nanospectra Bioscience, Inc). While the data is compelling, unfortunately the fundamentals of GNP heating are not entirely understood. For example, there are large discrepancies in the experimentally measured photothermal efficiency of GNPs (4, 5). Furthermore, lumped models of GNP heating in solution, by using small volume of GNP solution (4, 5), or stirring the solution (6), neglecting the variation of heat absorption throughout a system require improvement. In reality, the GNPs will attenuate the laser beam as it passes through the GNP host medium. GNPs at different locations will absorb different amount of laser energy and hence have different heat generation.

scholarly journals Import of fructose bisphosphate aldolase into the glycosomes of Trypanosoma brucei.

1987 ◽  
Vol 105 (6) ◽  
pp. 2649-2654 ◽  
Author(s):  
C E Clayton
Keyword(s):  
Trypanosoma Brucei ◽  
Peptide Mapping ◽  
Tsetse Fly ◽  
In Vitro Translation ◽  
Fructose Bisphosphate ◽  
Structural Differences ◽  
Fructose Bisphosphate Aldolase ◽  
Made In

The glycolytic enzymes of Trypanosomatids are compartmentalized within peroxisome-like microbodies called glycosomes. Fructose bisphosphate aldolase is synthesized on free polysomes and imported into glycosomes within 5 min. Peptide mapping reveals no primary structural differences between the in vivo-synthesized protein and that made in vitro from a synthetic template. However, native aldolase from glycosomes is partially protease resistant, whereas the in vitro translation product is not. Pulse-chase results indicate that aldolase in bloodstream trypanosomes has a much longer half-life than in the procyclic tsetse fly form.

Synthetic Studies with the Brevicidine and Laterocidine Lipopeptide Antibiotics Including Analogues with Enhanced Properties and in vivo Efficacy

2022 ◽  
Author(s):  
Karol Al-Ayed ◽  
Ross D. Ballantine ◽  
Michael Hoekstra ◽  
Samantha Bann ◽  
Charlotte Wesseling ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Solid Phase ◽  
Hydrolytic Stability ◽  
Attractive Alternative ◽  
Vitro Assay ◽  
Gram Negative ◽  
Lipopeptide Antibiotics ◽  
Synthetic Routes

Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, and a lipidated N-terminus, these lipopeptides exhibit potent and selective activity against Gram-negative pathogens, including polymyxin-resistant isolates. Given the low amounts of brevicidine and laterocidine accessible by fermentation of the producing microorganisms, synthetic routes to these lipopeptides present an attractive alternative. We here report the convenient solid-phase syntheses of both brevicidine and laterocidine and confirm their potent anti-Gram-negative activities. The synthetic routes developed also provide convenient access to novel structural analogues of both brevicidine and laterocidine that display improved hydrolytic stability while maintaining potent antibacterial activity in both in vitro assay and in vivo infection models.

scholarly journals Alteration in proportions of histone H1 variants during the differentiation of murine erythroleukaemic cells

1992 ◽  
Vol 288 (3) ◽  
pp. 747-751 ◽  
Author(s):  
W Helliger ◽  
H Lindner ◽  
O Grübl-Knosp ◽  
B Puschendorf
Keyword(s):  
Sodium Butyrate ◽  
Gel Electrophoresis ◽  
Histone H1 ◽  
Dimethyl Sulphoxide ◽  
Strong Increase ◽  
Reverse Phase ◽  
One Dimensional ◽  
Modest Increase

We have investigated the changes in the relative amounts of histone H1 zero and all five H1 variants during the differentiation in vitro of Friend erythroleukaemic cells. Three different agents were used as inducers of differentiation: dimethyl sulphoxide, hexamethylenebisacetamide and sodium butyrate. By applying a combination of reverse-phase h.p.l.c. and one-dimensional gel electrophoresis we observed that, during differentiation in vitro, (1) the relative amount of each subtype changes upon induction and that (2) dimethyl sulphoxide and hexamethylenebisacetamide produce a similar histone H1 pattern with a strong increase in histones H1 zero and H1c, a modest increase in histone H1e and a decrease in the relative amounts of histone H1a, H1b and H1d, whereas butyrate induces a different pattern, particularly with respect to both histones H1c and H1e: H1c increased slightly, and H1e strongly, during differentiation. These results are compared with changes in the histone H1 pattern during differentiation in vivo in the mouse [Lennox & Cohen (1983) J. Biol. Chem. 258, 262-268] and in the rat [Pina, Martinez & Suau (1987) Eur. J. Biochem. 164, 71-76], and similarities and deviations are discussed.

scholarly journals In vivo and in vitro complexes of activated protein C with two inhibitors in baboons

Blood ◽  
1991 ◽  
Vol 77 (8) ◽  
pp. 1754-1760 ◽  
Author(s):  
F Espana ◽  
A Gruber ◽  
MJ Heeb ◽  
SR Hanson ◽  
LA Harker ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Immunoblotting Analysis ◽  
Low Concentrations ◽  
Alpha 1 Antitrypsin ◽  
Formation Of Complexes

In vivo complex formation of activated protein C with protein C inhibitor (APC-PCI) and with alpha 1-antitrypsin (APC-alpha 1AT) following infusion of 0.25 or 1.0 mg APC/kg in 1 hour into baboons was studied using immunoblotting and sandwich enzyme-linked immunosorbent assay (ELISA)s. Before APC infusion, detectable plasma levels (about 30 ng/mL) of APC-alpha 1AT complex were found in the baboon plasma. At the lower APC dose, APC-PCI and APC-alpha 1AT complex levels were 1.4 +/- 0.3 (mean +/- SD) and 0.8 +/- 0.1 microgram/mL after 1 hour of infusion. At the higher APC dose, the APC-PCI level was similar to the APC-alpha 1AT level during the first 30 minutes, but after 1 hour of infusion the APC-alpha 1AT level was higher than the APC-PCI level, reaching 4.1 +/- 1.2 and 2.9 +/- 1.2 microgram/mL, respectively. After 24 hours, complex levels had returned to basal conditions. During infusion of protein C (1.0 mg/kg in 1 hour), both complexes were detected in low concentrations. Following bolus injection of APC, half- lives (t1/2) for APC and APC-PCI and APC-alpha 1AT complexes of 10, 40, and 140 minutes, respectively, were observed. After 1-hour incubation with 2.5 micrograms/mL APC, baboon plasma contained 1.0 +/- 0.2 and 0.8 +/- 0.1 microgram/mL of APC-PCI and APC-alpha 1AT, respectively. Addition of 10 micrograms/mL APC to baboon plasma yielded 2.5 and 2.4 micrograms/mL APC-PCI and APC-alpha 1AT after 1 hour, respectively. Immunoblotting analysis also showed in vivo formation of complexes of APC with an auxilliary inhibitor but not in vitro in citrated plasma. These data show that both PCI and alpha 1AT are physiologic inhibitors of APC and suggest that when PCI is depleted by a high dose of APC, alpha 1AT becomes the major inhibitor of APC.

scholarly journals Expansion of gamma-butyrolactone signaling molecule biosynthesis to phosphotriester natural products

2020 ◽  
Author(s):  
Yuta Kudo ◽  
Takayoshi Awakawa ◽  
Yi-Ling Du ◽  
Peter A. Jordan ◽  
Kaitlin E. Creamer ◽  
...  
Keyword(s):  
Natural Products ◽  
Gene Clusters ◽  
Biosynthetic Gene Clusters ◽  
Physiological Processes ◽  
Marine Actinomycete ◽  
Structural Differences ◽  
Species Specific ◽  
Gamma Butyrolactone

AbstractBacterial hormones, such as the iconic gamma-butyrolactone A-factor, are essential signaling molecules that regulate diverse physiological processes, including specialized metabolism. These low molecular weight compounds are common in Streptomyces species and display species-specific structural differences. Recently, unusual gamma-butyrolactone natural products called salinipostins were isolated from the marine actinomycete genus Salinispora based on their anti-malarial properties. As the salinipostins possess a rare phosphotriester motif of unknown biosynthetic origin, we set out to explore its construction by the widely conserved 9-gene spt operon in Salinispora species. We show through a series of in vivo and in vitro studies that the spt gene cluster dually encodes the saliniphostins and newly identified A-factor-like gamma-butyrolactones (Sal-GBLs). Remarkably, homologous biosynthetic gene clusters are widely distributed amongst many actinomycete genera, including Streptomyces, suggesting the significance of this operon in bacteria.

P–661 Comparative assessment of the structural features of human follicle-stimulating hormone in products from multiple markets

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
L Manzi ◽  
L Colarusso ◽  
F D’Angelo ◽  
D Drovandi ◽  
L Iozzino ◽  
...  
Keyword(s):  
Half Life ◽  
Follicle Stimulating Hormone ◽  
Structural Features ◽  
Delayed Response ◽  
Efficacy And Safety ◽  
Glycosylation Profile ◽  
Structural Differences ◽  
Stimulating Hormone

Abstract Study question The aim of the study is to explore the structural differences occurring in recombinant human follicle-stimulating hormone alfa (r-hFSH- α), originator and its biosimilars, from various countries. Summary answer When compared with r-hFSH-α originator (Gonal-f), its biosimilars presented structural differences, namely Primapur showed a significant different glycosylation profile. What is known already FSH is part of cystine knot growth factor superfamily and plays a central role in reproduction, as FSH stimulates follicular development and estrogen synthesis. R-hFSH- α is commonly used in assisted reproductive technologies to achieve multifollicular development. At the present r-hFSH- α biosimilars are available in Europe and other regions. R-hFSH-α is a complex glycoprotein, that possesses several structural features critical for its efficacy and safety1–2. Glycosylation profile is one of the most impactful attributes of the molecule defining a moiety of FSH isoforms with impact on its biological net effect3. Efficacy and safety of r-hFSH- α are strictly correlated with glycoforms’ composition3–8. Study design, size, duration At least two different batches of each r-hFSH- α originator and its biosimilars have been included in the study. Participants/materials, setting, methods The structural features of products from six different marketed r-hFSH α (Gonal-f, Primapur, Folisurge Intas, Corneumon, Jin Sai Heng, Follitrope LG) have been investigated with a variety of analytical techniques in order to evaluate the presence of molecular differences, which could have a severe impact on the efficacy and safety of the product. The attributes which have been investigated in-depth include primary, secondary and tertiary structure as well as post-translational modifications (PTMs), including glycosylation and contaminants. Main results and the role of chance All r-hFSH- α biosimilars analyzed presented differences compared to the originator. We firstly investigated Primapur and found significant differences regarding multiple structural attributes, particularly in the glycosylation profile. Gonal-f exhibited lower glycan branching, expressed by an A-index* of 2.5, while Primapur showed an A-index of 2.4. Furthermore, Primapur showed a lower level of sialylation in comparison with Gonal-f, as measured by their respective S-index* of 1.8 and 2.1. FSH glycosylation exhibits both macroheterogeneity and microheterogeneity, impacting both FSH protein’s half-life and affinity with the follicle-stimulating hormone receptor (FSHR). Antennarity, representing FSH microheterogeneity, influence r-hFSH-α activity since it has been shown that bulky and extended glycans may take longer to fit into the FSHR cavity compared to less sterically hindering glycans, resulting in a delayed response 7,8.Additionaly, sialylation has been shown in-vivo to correlate with plasma half-life and effect on granulosa cells proliferation 1,2,3. The slower clearance of highly sialylated r-hFSH has been shown to lead to a higher in-vivo activity, despite the lower in-vitro bioactivity 1,2,3. *A-index and S-index express respectively a measure of the number of antennae and sialic acid per glycan. Final values are generated from many relative abundances normalized to 100, highlighting the significance of small numerical differences. Limitations, reasons for caution More batches should be tested for each product. The authors are presenting full characterization of only one of the biosimilars since the rest of the products are under characterization. Wider implications of the findings: r-hFSH-α originator and its biosimilar showed differences in terms of glycosylation profile that is well known as the major protein characteristic impacting FSH activity as extensively demonstrated in in-vivo and in-vitro models. This structural difference could have impact also on product efficacy and safety. Trial registration number ‘not applicable’

scholarly journals Toxicity of Zero- and One-Dimensional Carbon Nanomaterials

Nanomaterials ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 1214 ◽  
Author(s):  
Iruthayapandi Selestin Raja ◽  
Su-Jin Song ◽  
Moon Sung Kang ◽  
Yu Bin Lee ◽  
Bongju Kim ◽  
...  
Keyword(s):  
Quantum Dot ◽  
Carbon Nanomaterials ◽  
Volume Ratio ◽  
In Vivo Studies ◽  
In Vitro Toxicity ◽  
One Dimensional ◽  
Multi Walled Carbon Nanotubes ◽  
Living Organisms

The zero (0-D) and one-dimensional (1-D) carbon nanomaterials have gained attention among researchers because they exhibit a larger surface area to volume ratio, and a smaller size. Furthermore, carbon is ubiquitously present in all living organisms. However, toxicity is a major concern while utilizing carbon nanomaterials for biomedical applications such as drug delivery, biosensing, and tissue regeneration. In the present review, we have summarized some of the recent findings of cellular and animal level toxicity studies of 0-D (carbon quantum dot, graphene quantum dot, nanodiamond, and carbon black) and 1-D (single-walled and multi-walled carbon nanotubes) carbon nanomaterials. The in vitro toxicity of carbon nanomaterials was exemplified in normal and cancer cell lines including fibroblasts, osteoblasts, macrophages, epithelial and endothelial cells of different sources. Similarly, the in vivo studies were illustrated in several animal species such as rats, mice, zebrafish, planktons and, guinea pigs, at various concentrations, route of administrations and exposure of nanoparticles. In addition, we have described the unique properties and commercial usage, as well as the similarities and differences among the nanoparticles. The aim of the current review is not only to signify the importance of studying the toxicity of 0-D and 1-D carbon nanomaterials, but also to emphasize the perspectives, future challenges and possible directions in the field.

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