Functional design of glycan-conjugated molecules using a chemoenzymatic approach

2021 ◽  
Author(s):  
Makoto Ogata
Keyword(s):  
Molecular Weight ◽  
Large Scale ◽  
Biological Activities ◽  
Natural Compounds ◽  
Low Molecular Weight ◽  
Functional Design ◽  
Enzymatic Method ◽  
Conjugated Molecules ◽  
Design Synthesis ◽  
And Function

Abstract Carbohydrates play important and diverse roles in the fundamental processes of life. We have established a method for accurately and a large scale synthesis of functional carbohydrates with diverse properties using a unique enzymatic method. Furthermore, various artificial glycan-conjugated molecules have been developed by adding these synthetic carbohydrates to macromolecules and to middle and low molecular weight molecules with different properties. These glycan-conjugated molecules have biological activities comparable to or higher than those of natural compounds, and present unique functions. In this review, several synthetic glycan-conjugated molecules are taken as examples to show design, synthesis and function.

Circulating Activities During Constant Infusion of Heparin or a Low Molecular Weight Derivative (Enoxaparine): Failure to Demonstrate any Circadian Variations

1987 ◽  
Vol 58 (04) ◽  
pp. 1068-1072 ◽  
Author(s):  
P Toulon ◽  
J F Vitoux ◽  
C Leroy ◽  
T Lecomte ◽  
M Roncato ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Circadian Rhythm ◽  
Biological Activities ◽  
Constant Infusion ◽  
Low Molecular Weight ◽  
Circadian Variations ◽  
Heparin Cofactor Ii ◽  
Heparin Infusion ◽  
Chromogenic Assay ◽  
Heparin Affinity

SummaryWe compared in six patients successively treated with an unfractionated heparin (UFH) and a low molecular weight heparin (LMWH) the variations in plasma anti-Xa activity, measured in a chromogenic assay, during a 36 h constant infusion. The values varied in a wider range during UHF infusion, but remained in the therapeutic range except once in one patient. No circadian rhythm could be demonstrated in our six patients. LMWH infusion yielded very constant anti-Xa circulating activities. In both cases, there were no significant modifications of three proteins with high heparin affinity (antithrombin III, heparin cofactor II, histidine-rich glycoprotein).Our results suggest that the circadian rhythm of the biological activities previously observed in patients treated with constant heparin infusion using clotting method is due to other factors than heparin itself.

Polyamine metabolism and function

1982 ◽  
Vol 243 (5) ◽  
pp. C212-C221 ◽  
Author(s):  
A. E. Pegg ◽  
P. P. McCann
Keyword(s):  
Molecular Weight ◽  
Tissue Growth ◽  
Polyamine Metabolism ◽  
Organic Cations ◽  
Low Molecular Weight ◽  
Polyamine Biosynthesis ◽  
Polyamine Content ◽  
And Function ◽  
Specific Inhibitors

Polyamines are ubiquitous organic cations of low molecular weight. The content of these amines is closely regulated by the cell according to the state of growth. The reactions responsible for the biosynthesis and interconversion of the polyamines and their precursor putrescine are described and the means by which polyamine content can be varied in response to exogenous stimuli are discussed. The role of polyamines in the cell cycle, cell division, tissue growth, and differentiation is considered. Recent studies using highly specific inhibitors of polyamine biosynthesis such as alpha-difluoromethylornithine to prevent accumulation of polyamines have indicated that the synthesis of polyamines is intimately associated with these processes. Such inhibitors have great potential for investigation of the cellular role of polyamines.

Biological activity of partially purified low molecular weight luteinizing hormone binding inhibitor in porcine follicular fluids

1993 ◽  
Vol 128 (1) ◽  
pp. 88-94 ◽  
Author(s):  
Nobuyoshi Kokawa ◽  
Mareo Yamoto ◽  
Kenichi Furukawa ◽  
Ryosuke Nakano
Keyword(s):  
Molecular Weight ◽  
Luteinizing Hormone ◽  
Competitive Inhibition ◽  
Biological Activities ◽  
Partial Purification ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Hormone Binding ◽  
Dose Dependent ◽  
Follicular Fluids

We performed partial purification of low molecular weight luteinizing hormone binding inhibitor from porcine follicular fluids and examined its biological activities. Following ultrafiltration, gel filtration and anion exchange of the pooled porcine follicular fluids, low molecular weight fractions (500–10,000 MW) inhibited [125I]hLH binding to porcine granulosa cells in a dose-dependent manner. The binding inhibition kinetics study revealed that the luteinizing hormone binding inhibitor may indicate a non-competitive inhibition with [125I]hLH binding. In vitro bioassay using adult mouse testicular interstitial cells revealed that the partially purified luteinizing hormone binding inhibitor reduced ovine LH-stimulated testosterone and cAMP production in a dose-dependent manner, whereas the luteinizing hormone binding inhibitor did not affect basal production of testosterone and cAMP. The inhibitory activity was heat stable and did not disappear with activated charcoal adsorption. The results of the present study suggest that the luteinizing hormone binding inhibitor may play an important role as an ovarian non-steroidal regulator modulating the receptor binding of LH and LH-mediated steroidogenesis.

scholarly journals A Deep Learning-Based Approach for Identifying the Medicinal Uses of Plant-Derived Natural Compounds

2020 ◽  
Vol 11 ◽  
Author(s):  
Sunyong Yoo ◽  
Hyung Chae Yang ◽  
Seongyeong Lee ◽  
Jaewook Shin ◽  
Seyoung Min ◽  
...  
Keyword(s):  
Deep Learning ◽  
Large Scale ◽  
Natural Compound ◽  
Biological Activities ◽  
Natural Compounds ◽  
Model Potential ◽  
Medicinal Uses ◽  
Large Scale Analysis ◽  
Investigational Drugs

Medicinal plants and their extracts have been used as important sources for drug discovery. In particular, plant-derived natural compounds, including phytochemicals, antioxidants, vitamins, and minerals, are gaining attention as they promote health and prevent disease. Although several in vitro methods have been developed to confirm the biological activities of natural compounds, there is still considerable room to reduce time and cost. To overcome these limitations, several in silico methods have been proposed for conducting large-scale analysis, but they are still limited in terms of dealing with incomplete and heterogeneous natural compound data. Here, we propose a deep learning-based approach to identify the medicinal uses of natural compounds by exploiting massive and heterogeneous drug and natural compound data. The rationale behind this approach is that deep learning can effectively utilize heterogeneous features to alleviate incomplete information. Based on latent knowledge, molecular interactions, and chemical property features, we generated 686 dimensional features for 4,507 natural compounds and 2,882 approved and investigational drugs. The deep learning model was trained using the generated features and verified drug indication information. When the features of natural compounds were applied as input to the trained model, potential efficacies were successfully predicted with high accuracy, sensitivity, and specificity.

scholarly journals CD80 Expression Correlates with IL-6 Production in THP-1-Like Macrophages Costimulated with LPS and Dialyzable Leukocyte Extract (Transferon®)

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Alexis P. Jiménez-Uribe ◽  
Hugo Valencia-Martínez ◽  
Gregorio Carballo-Uicab ◽  
Luis Vallejo-Castillo ◽  
Emilio Medina-Rivero ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Flow Cytometry ◽  
Viral Infections ◽  
Surface Expression ◽  
Low Molecular Weight ◽  
Activated Macrophages ◽  
Therapeutic Properties ◽  
And Function ◽  
Complex Drug ◽  
Stimulation Of

Transferon® is a complex drug based on a mixture of low molecular weight peptides. This biotherapeutic is employed as a coadjuvant in clinical trials of several diseases, including viral infections and allergies. Given that macrophages play key roles in pathogen recognition, phagocytosis, processing, and antigen presentation, we evaluated the effect of Transferon® on phenotype and function of macrophage-like cells derived from THP-1 monocytes. We determined the surface expression of CD80 and CD86 by flow cytometry and IL-1β, TNF-α, and IL-6 levels by ELISA. Transferon® alone did not alter the steady state of PMA-differentiated macrophage-like THP-1 cells. On the contrary, simultaneous stimulation of cells with Transferon® and LPS elicited a significant increase in CD80 (P≤0.001) and CD86 (P≤0.001) expression, as well as in IL-6 production (P≤0.05) compared to the LPS control. CD80 expression and IL-6 production exhibited a positive correlation (r=0.6, P≤0.05) in cells exposed to Transferon® and LPS. Our results suggest that the administration of Transferon® induces the expression of costimulatory molecules and the secretion of cytokines in LPS-activated macrophages. Further studies are necessary to determine the implication of these findings in the therapeutic properties of Transferon®.

scholarly journals Selective Suppression of Cell Growth and Programmed Cell Death-Ligand 1 Expression in HT1080 Fibrosarcoma Cells by Low Molecular Weight Fucoidan Extract

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 421 ◽  
Author(s):  
Kiichiro Teruya ◽  
Yoshihiro Kusumoto ◽  
Hiroshi Eto ◽  
Noboru Nakamichi ◽  
Sanetaka Shirahata
Keyword(s):  
Molecular Weight ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Cells ◽  
Biological Activities ◽  
Immune Surveillance ◽  
Selective Inhibition ◽  
Low Molecular Weight ◽  
Fibrosarcoma Cells ◽  
Self Protection

Low molecular weight fucoidan extract (LMF), prepared by an abalone glycosidase digestion of a crude fucoidan extracted from Cladosiphon novae-caledoniae Kylin, exhibits various biological activities, including anticancer effect. Various cancers express programmed cell death-ligand 1 (PD-L1), which is known to play a significant role in evasion of the host immune surveillance system. PD-L1 is also expressed in many types of normal cells for self-protection. Previous research has revealed that selective inhibition of PD-L1 expressed in cancer cells is critical for successful cancer eradication. In the present study, we analyzed whether LMF could regulate PD-L1 expression in HT1080 fibrosarcoma cells. Our results demonstrated that LMF suppressed PD-L1/PD-L2 expression and the growth of HT1080 cancer cells and had no effect on the growth of normal TIG-1 cells. Thus, LMF differentially regulates PD-L1 expression in normal and cancer cells and could serve as an alternative complementary agent for treatment of cancers with high PD-L1 expression.

scholarly journals Determination of the Structural Integrity and Stability of Polysialic Acid during Alkaline and Thermal Treatment

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 165
Author(s):  
Bastian Bartling ◽  
Johanna S. Rehfeld ◽  
Daniel Boßmann ◽  
Ingo de Vries ◽  
Jörg Fohrer ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Large Scale ◽  
Polysialic Acid ◽  
Alkaline Solutions ◽  
Low Molecular Weight ◽  
Outer Cell ◽  
Scale Production ◽  
Thermal Hydrolysis ◽  
E Coli ◽  
Chain Lengths

Polysialic acid (polySia) is a linear homopolymer of varying chain lengths that exists mostly on the outer cell membrane surface of certain bacteria, such as Escherichia coli (E. coli) K1. PolySia, with an average degree of polymerization of 20 (polySia avDP20), possesses material properties that can be used for therapeutic applications to treat inflammatory neurodegenerative diseases. The fermentation of E. coli K1 enables the large-scale production of endogenous long-chain polySia (DP ≈ 130) (LC polySia), from which polySia avDP20 can be manufactured using thermal hydrolysis. To ensure adequate biopharmaceutical quality of the product, the removal of byproducts and contaminants, such as endotoxins, is essential. Recent studies have revealed that the long-term incubation in alkaline sodium hydroxide (NaOH) solutions reduces the endotoxin content down to 3 EU (endotoxin units) per mg, which is in the range of pharmaceutical applications. In this study, we analyzed interferences in the intramolecular structure of polySia caused by harsh NaOH treatment or thermal hydrolysis. Nuclear magnetic resonance (NMR) spectroscopy revealed that neither the incubation in an alkaline solution nor the thermal hydrolysis induced any chemical modification. In addition, HPLC analysis with a preceding 1,2-diamino-4,5-methylenedioxybenzene (DMB) derivatization demonstrated that the alkaline treatment did not induce any hydrolytic effects to reduce the maximum polymer length and that the controlled thermal hydrolysis reduced the maximum chain length effectively, while cost-effective incubation in alkaline solutions had no adverse effects on LC polySia. Therefore, both methods guarantee the production of high-purity, low-molecular-weight polySia without alterations in the structure, which is a prerequisite for the submission of a marketing authorization application as a medicinal product. However, a specific synthesis of low-molecular-weight polySia with defined chain lengths is only possible to a limited extent.

Design, Synthesis, and Evaluation of a Low-Molecular-Weight 11C-Labeled Tetrazine for Pretargeted PET Imaging Applying Bioorthogonal in Vivo Click Chemistry

2016 ◽  
Vol 27 (7) ◽  
pp. 1707-1712 ◽  
Author(s):  
Christoph Denk ◽  
Dennis Svatunek ◽  
Severin Mairinger ◽  
Johann Stanek ◽  
Thomas Filip ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Click Chemistry ◽  
Pet Imaging ◽  
Low Molecular Weight ◽  
Design Synthesis

scholarly journals Bioorganic studies on the venom from duckbill platypus

2012 ◽  
Vol 84 (6) ◽  
pp. 1317-1328 ◽  
Author(s):  
Masaki Kita
Keyword(s):  
Molecular Weight ◽  
Guinea Pig ◽  
Structure And Function ◽  
Low Molecular Weight ◽  
Tissue Kallikrein ◽  
Guinea Pig Ileum ◽  
Porcine Pancreas ◽  
Human Neuroblastoma ◽  
Ornithorhynchus Anatinus ◽  
And Function

Venomous mammals are rare, and only a few species in the orders Insectivora and Monotremata produce toxic venom. Among them, the duckbill platypus (Ornithorhynchus anatinus) is one of the two venomous Australian mammals. The adult male platypus carries a spur on each hind leg, which it uses to inject competitors with poison. However, the structure and function of the poison’s active compounds are still imcompletely characterized. We found that crude platypus venom produced potent Ca2+influx in human neuroblastoma IMR-32 cells. Guided by this assay, we identified 11 unique peptides, including peptide H–His–Asp–His–Pro–Asn–Pro–Arg–OH, which coincided with the N-terminal domain residues ofOrnithorhynchusvenom C-type natriuretic peptide (OvCNP). This heptapeptide induced a significant increase in [Ca2+]iin IMR-32 cells at 75 μM; had relatively specific affinities for glutamate, histamine, and GABAAreceptors; and facilitated neurogenic twitching in guinea pig ileum specimens at 30 μM. We also established that its proteinous venom fraction strongly hydrolyzed Pro–Phe–Arg–MCA and cleaved a human low-molecular-weight kininogen (LK), similar to porcine pancreas kallikrein. These results strongly indicated that platypus venom contains tissue kallikrein-like protease(s), and its proteolytic activity might synergistically contribute to toxicity through the specific cleavage of other venom constituents.

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