Modified Aminoglycosides Bind Nucleic Acids in High-Molecular-Weight Complexes

Aminoglycosides represent a large group of antibiotics well known for their ability to target the bacterial ribosome. In studying 6”-substituted variants of the aminoglycoside tobramycin, we serendipitously found that compounds with C12 or C14 linear alkyl substituents potently inhibit reverse transcription in vitro. Initial observations suggested specific inhibition of reverse transcriptase. However, further analysis showed that these and related compounds bind nucleic acids with high affinity, forming high-molecular weight complexes. Stable complex formation is observed with DNA or RNA in single- or double-stranded form. Given the amphiphilic nature of these aminoglycoside derivatives, they likely form micelles and/or vesicles with surface-bound nucleic acids. Hence, these compounds may be useful tools to localize nucleic acids to surfaces or deliver nucleic acids to cells or organelles.

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The Effect of Dextran of Various Molecular Weight on the Coagulation in Dogs

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654535 ◽

1961 ◽

Vol 06 (01) ◽

pp. 015-024 ◽

Cited By ~ 32

Author(s):

Sven Erik Bergentz ◽

Oddvar Eiken ◽

Inga Marie Nilsson

Keyword(s):

Molecular Weight ◽

Body Weight ◽

High Molecular Weight ◽

Bleeding Time ◽

Factor Vii ◽

Low Molecular Weight ◽

Factor V ◽

Coagulation Mechanism ◽

Coagulation Defects

Summary1. Infusions of low molecular weight dextran (Mw = 42 000) to dogs in doses of 1—1.5 g per kg body weight did not produce any significant changes in the coagulation mechanism.2. Infusions of high molecular weight dextran (Mw = 1 000 000) to dogs in doses of 1—1.5 g per kg body weight produced severe defects in the coagulation mechanism, namely prolongation of bleeding time and coagulation time, thrombocytopenia, pathological prothrombin consumption, decrease of fibrinogen, prothrombin and factor VII, factor V and AHG.3. Heparin treatment of the dogs was found to prevent the decrease of fibrinogen, prothrombin and factor VII, and factor V otherwise occurring after injection of high molecular weight dextran. Thrombocytopenia was not prevented.4. In in vitro experiments an interaction between fibrinogen and dextran of high and low molecular weight was found to take place in systems comprising pure fibrinogen. No such interaction occurred in the presence of plasma.5. It is concluded that the coagulation defects induced by infusions of high molecular weight dextran are due to intravascular coagulation.

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Novel concatameric heparin-binding peptides reverse heparin and low-molecular-weight heparin anticoagulant activities in patient plasma in vitro and in rats in vivo

Blood ◽

10.1182/blood-2003-07-2334 ◽

2004 ◽

Vol 103 (4) ◽

pp. 1356-1363 ◽

Cited By ~ 30

Author(s):

Barbara P. Schick ◽

David Maslow ◽

Adrianna Moshinski ◽

James D. San Antonio

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Tandem Repeats ◽

Factor Xa ◽

Low Molecular Weight ◽

Heparin Binding ◽

High Affinity ◽

Binding Peptides

Abstract Patients given unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) for prophylaxis or treatment of thrombosis sometimes suffer serious bleeding. We showed previously that peptides containing 3 or more tandem repeats of heparin-binding consensus sequences have high affinity for LMWH and neutralize LMWH (enoxaparin) in vivo in rats and in vitro in citrate. We have now modified the (ARKKAAKA)n tandem repeat peptides by cyclization or by inclusion of hydrophobic tails or cysteines to promote multimerization. These peptides exhibit high-affinity binding to LMWH (dissociation constant [Kd], ≈ 50 nM), similar potencies in neutralizing anti–Factor Xa activity of UFH and enoxaparin added to normal plasma in vitro, and efficacy equivalent to or greater than protamine. Peptide (ARKKAAKA)3VLVLVLVL was most effective in all plasmas from enoxaparin-treated patients, and was 4- to 20-fold more effective than protamine. Several other peptide structures were effective in some patients' plasmas. All high-affinity peptides reversed inhibition of thrombin-induced clot formation by UFH. These peptides (1 mg/300 g rat) neutralized 1 U/mL anti–Factor Xa activity of enoxaparin in rats within 1 to 2 minutes. Direct blood pressure and heart rate measurements showed little or no hemodynamic effect. These heparin-binding peptides, singly or in combination, are potential candidates for clinical reversal of UFH and LMWH in humans.

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Physicochemical and Antifungal Properties of Clotrimazole in Combination with High-Molecular Weight Chitosan as a Multifunctional Excipient

Marine Drugs ◽

10.3390/md18120591 ◽

2020 ◽

Vol 18 (12) ◽

pp. 591

Author(s):

Bożena Grimling ◽

Bożena Karolewicz ◽

Urszula Nawrot ◽

Katarzyna Włodarczyk ◽

Agata Górniak

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Weight Ratio ◽

Scanning Calorimetry ◽

Minimal Inhibitory Concentrations ◽

Dissolution Tests ◽

Effective Combination ◽

The Impact ◽

High Molecular Weight Chitosan

Chitosans represent a group of multifunctional drug excipients. Here, we aimed to estimate the impact of high-molecular weight chitosan on the physicochemical properties of clotrimazole–chitosan solid mixtures (CL–CH), prepared by grinding and kneading methods. We characterised these formulas by infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry, and performed in vitro clotrimazole dissolution tests. Additionally, we examined the antifungal activity of clotrimazole–chitosan mixtures against clinical Candida isolates under neutral and acid conditions. The synergistic effect of clotrimazole and chitosan S combinations was observed in tests carried out at pH 4 on Candida glabrata strains. The inhibition of C. glabrata growth reached at least 90%, regardless of the drug/excipient weight ratio, and even at half of the minimal inhibitory concentrations of clotrimazole. Our results demonstrate that clotrimazole and high-molecular weight chitosan could be an effective combination in a topical antifungal formulation, as chitosan acts synergistically with clotrimazole against non-albicans candida strains.

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Identity and Origin of the ATPase activity associated with neuronal microtubules. I. The ATPase activity is associated with membrane vesicles.

The Journal of Cell Biology ◽

10.1083/jcb.96.5.1298 ◽

1983 ◽

Vol 96 (5) ◽

pp. 1298-1305 ◽

Cited By ~ 13

Author(s):

D B Murphy ◽

R R Hiebsch ◽

K T Wallis

Keyword(s):

Molecular Weight ◽

Atpase Activity ◽

High Molecular Weight ◽

Brain Tissue ◽

Membrane Vesicles ◽

Microtubule Associated Proteins ◽

In Vitro Assembly ◽

Microtubule Protein ◽

Associated Proteins

Microtubule protein purified from brain tissue by cycles of in vitro assembly-disassembly contains ATPase activity that has been postulated to be associated with microtubule-associated proteins (MAPs) and therefore significant for studies of microtubule-dependent motility. In this paper we demonstrate that greater than 90% of the ATPase activity is particulate in nature and may be derived from contaminating membrane vesicles. We also show that the MAPs (MAP-1, MAP-2, and tau factors) and other high molecular weight polypeptides do not contain significant amounts of ATPase activity. These findings do not support the concept of "brain dynein" or of MAPs with ATPase activity.

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Interaction of Streptococcus mutans Glucosyltransferases with Teichoic Acids

Infection and Immunity ◽

10.1128/iai.29.2.376-382.1980 ◽

1980 ◽

Vol 29 (2) ◽

pp. 376-382

Author(s):

H. K. Kuramitsu ◽

L. Wondrack ◽

M. McGuinness

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Streptococcus Mutans ◽

Teichoic Acid ◽

Lipoteichoic Acid ◽

Water Soluble ◽

Heat Inactivation ◽

Teichoic Acids ◽

Insoluble Glucan

The Streptococcus mutans GS5 glucosyltransferase activities (both water-soluble and -insoluble glucan-synthesizing fractions) were inhibited by purified lipoteichoic acid. In vitro sucrose-dependent colonization of smooth surfaces by strain GS5 was also markedly reduced in the presence of the amphipathic molecules. The inhibition of soluble glucan synthesis by lipoteichoic acid appeared to be competitive with respect to both sucrose and primer dextran T10. These inhibitory effects were dependent on the presence of the fatty acid components of lipoteichoic acid since deacylated lipoteichoic acids did not inhibit glucosyltransferase activity. However, the deacylated molecules did interact with the enzymes since deacylated lipoteichoic acid partially protected the enzyme activity against heat inactivation and also induced the formation of high-molecular-weight enzyme complexes from the soluble glucan-synthesizing fraction. The presence of teichoic acid in high-molecular-weight aggregates of glucosyltransferase isolated from the culture fluids of strain GS5 was suggested by the detection of polyglycerophosphate in these fractions. In addition to strain GS5, two other organisms containing polyglycerophosphate teichoic acids, Lactobacillus casei and Lactobacillus fermentum , were demonstrated to bind glucosyltransferase activity. These results are discussed relative to the potential role of teichoic acid-glucosyltransferase interactions in enzyme binding to the cell surface of S. mutans and the formation of high-molecular-weight enzyme aggregates in the culture fluids of the organism.

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Preparation of high-molecular weight and high-sulfate content chitosans and their potential antioxidant activity in vitro

Carbohydrate Polymers ◽

10.1016/j.carbpol.2005.04.007 ◽

2005 ◽

Vol 61 (2) ◽

pp. 148-154 ◽

Cited By ~ 97

Author(s):

Ronge Xing ◽

Song Liu ◽

Huahua Yu ◽

Zhanyong Guo ◽

Zhien Li ◽

...

Keyword(s):

Molecular Weight ◽

Antioxidant Activity ◽

High Molecular Weight ◽

Sulfate Content ◽

High Sulfate

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Pro-angiogenic effect of human kallikrein-related peptidase 12 (KLK12) in lung endothelial cells does not depend on kinin-mediated activation of B2 receptor

Biological Chemistry ◽

10.1515/hsz-2012-0291 ◽

2013 ◽

Vol 394 (3) ◽

pp. 385-391 ◽

Cited By ~ 11

Author(s):

Thomas Kryza ◽

Gilles Lalmanach ◽

Marion Lavergne ◽

Fabien Lecaille ◽

Pascale Reverdiau ◽

...

Keyword(s):

Molecular Weight ◽

Endothelial Cells ◽

High Molecular Weight ◽

High Molecular Weight Kininogen ◽

Kinin Receptor ◽

Angiogenic Effect ◽

Lung Endothelial Cells ◽

Carboxy Terminal

Abstract Kallikrein-12 (KLK12) may play an important role in angiogenesis modulating proangiogenic factor bioavailability and activating the kinin receptor B2 pathway. We studied whether KLK12 had an impact on angiogenesis and the activation of kinin receptor B2 results from the KLK12-dependent generation of kinins. KLK12 efficiently hydrolyzed high molecular weight kininogen, liberating a fragment containing the carboxy-terminal end of kinins. The kininogenase activity of KLK12 was poor, however, due to the cleavage resistance of the N-terminal side of the kinin sequence. A very low amount of kinins was accordingly released after in vitro incubation of high molecular weight kininogen with KLK12 and thus the proangiogenic activity of KLK12 in lung endothelial cells was not related to a kinin release.

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