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PubMed1983

Photoaffinity reagents for use with pepsin and other carboxyl proteases.

Two compounds have been designed to serve as photoaffinity reagents for use with carboxyl proteases. 1,2-Epoxy-3-(4'-azido-2'-nitrophenoxy)propane has been synthesized and shown to react with porcine pepsin in the same fashion as the traditional inhibitor 1,2-epoxy-3-(p-nitrophenoxy)propane, while p-azidophenacyl bromide is similar to other phenacyl bromides in its reaction with pepsin. In combination with p-azido-alpha-diazoacetophenone, previously shown to resemble alpha-diazo carbonyl reagents in its reaction with pepsin, photoaffinity analogs are now available for all three of the widely-used carboxyl protease inhibitors.

Affinity Labels↗
PubMed1982

Mode of action of 3-substituted propylamine cytotoxicity in culture cells.

Cytotoxic effects on MDBK cells of various 3-substituted propylamines, including spermine and spermidine, were tested in culture in the presence of calf serum, and the possible mode of action was studied from the viewpoint of oxidative deamination leading to acrolein formation. The compounds were roughly classified in two groups with IC50 values of 0.1 and 0.4 mM under the conditions used. Phenyl derivatives of 3-substituted propylamines, 3-benzylaminopropylamine, and polyamines were included in the first group with IC50 values of 0.1 mM, and acrolein was liberated from these compounds after incubation with bovine plasma amine oxidase. Alkyl derivatives of 3-substituted propylamines (with IC50 values of 0.4 mM), on the other hand, were unable to release acrolein after the oxidative deamination, which was further confirmed by a lack of liberation of acrolein from the authentic 3-butoxypropanal. These observations indicated that both the acrolein originating from the 3-substituted propanals, and the propanal as such, were possibly involved in manifestation of the cytotoxicity of the 3-substituted propylamines. Thus, spermine and spermidine may exert their cytotoxic effects on the cells in vitro by a combination of two mechanisms involving acrolein and oxidized polyamines.

1-Propanol↗
PubMed1993

The hydrolysis product of ICRF-187 promotes iron-catalysed hydroxyl radical production via the Fenton reaction.

d-1,2-Bis(3,5-dioxopiperazine-1-yl)propane (ICRF-187) (ADR-529) is a drug that ameliorates the cardiotoxicity of Adriamycin. The drug enters cells where hydrolysis leads to its diacid diamide product, dl-N,N'-dicarboxamidomethyl-N,N'-dicarboxymethyl-1,2-diamino propane (ICRF-198) (ADR-925), which is structurally similar to ethylenediaminetetraacetic acid (EDTA). The protective mechanism of ICRF-187 is unknown, but a plausible explanation is that ICRF-198 chelates iron intracellularly to prevent iron-dependent free radical reactions such as hydroxyl radical (.OH) production. We have compared Fe(ICRF-198) with Fe(EDTA) in its ability to promote .OH formation in several Fenton reaction systems. The Fenton reaction was studied with H2O2 and Fe2+ chelates or catalytic amounts of the iron chelates in the presence of Adriamycin radicals, paraquat radicals, superoxide anion radicals (O2-), and ascorbate as reducing species. .OH was detected with deoxyribose and dimethyl sulfoxide. The two methods gave comparable results. Fe(ICRF-198) was 80-100% as effective as Fe(EDTA) at promoting .OH production in the presence of the organic radicals and ascorbate, 30-70% in the presence of O2-, and 150% with non-cycling Fe2+. Fe(EDTA) is a more efficient catalyst of .OH production than physiological chelates such as ADP, ATP and citrate. Therefore, by comparing previous work which examined physiological chelates and Fe(EDTA) with the present work, Fe(ICRF-198) appears to be a better .OH catalyst than the physiological chelates. These results suggest that ICRF-198 generated in vivo from ICRF-187 would not protect against intracellular .OH production. They also imply that .OH production may not be as important in Adriamycin cardiotoxicity as other radical reactions, such as lipid peroxidation and thiol oxidation, that are inhibited by ICRF-198.

Ascorbic Acid↗
PubMed1996

Transgenic model for the discovery of novel human secretory non-pancreatic phospholipase A2 inhibitors.

Transgenic mice were created which overexpress human secretory non-pancreatic phospholipase A2 (sPLA2) pansomatically as a potential disease and drug-testing model. The mice were produced using a DNA construct in which the inducible mouse metallothionein gene promoter drives expression of a human sPLA2 minigene. High levels of sPLA2 were detected in several tissues by immunofluorescence localization. Expression in the testes caused hypospermia and male infertility. Circulating catalytically active sPLA2 could be induced to levels observed in patients undergoing a systemic inflammatory response but had no detectable effect on the mice. Therefore, these results suggest that sPLA2 hyperphospholipasemia alone may have only limited pathophysiological consequences. We further show that 3-[3-acetamide-1-benzyl-2-ethylindolyl-5-oxy]propane phosphonic acid LY311727), a potent new inhibitor of phospholipase A2 catalysis developed by our group, dramatically suppresses the circulating enzyme activity in these animals whereas 3-[3-acetamide-1-benzyl-2-propylindolyl-5-oxy]propane phosphonic acid (LY314024), a substantially less potent LY311727 analog, is without effect. These later results thus motivate the further development of this compound as a potential new therapeutic agent and valuable research tool.

Animals↗
PubMed1984

Rapid method of extraction of antibodies from hen egg yolk.

Antibodies were raised in laying hens and isolated from the yolk of their eggs by precipitation with precooled (-20 degrees C) propane-2-ol and removing lipid material with propane-2-ol and acetone. The dried precipitate was extracted with phosphate buffer and shown to contain IgG antibodies and a small amount of additional protein. By Ouchterlony gel diffusion and rocket immunoelectrophoresis, the concentration and quality of specific antibodies in the extracts were comparable to those found in the serum of rabbits or to the IgG separated from yolk by other methods. The new isolation procedure is rapid, reliable and convenient.

Animals↗
PubMed1988

Uptake in brain and neurophysiological activity of two lipid esters of gamma-aminobutyric acid.

Two lipid esters of gamma-aminobutyric acid (GABA), 1-linolenoyl-2,3-bis(4-aminobutyryl)propane-1,2,3-triol and 1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol, were found to have brain uptake indices of greater than 30% using the single-pass carotid artery injection technique. Both compounds produced dose-dependent inhibition of the evoked population spike in slices of rat hippocampus maintained in vitro. This effect was blocked reversibly by picrotoxin. The magnitude of the inhibition produced by the lipid esters of GABA was comparable to that of similar doses of GABA, but for both compounds the duration of the effect was at least 10 times longer than that produced by GABA. These data are consistent with the idea that the lipid esters of GABA can effectively penetrate the blood-brain barrier and act as prodrugs for the delivery of GABA to the central nervous system.

Action Potentials↗
PubMed1990

gamma-Aminobutyric acid antagonism produced by an organophosphate-containing combustion product.

Results from [35S]t-butylbicyclophosphorothionate (TBPS) binding and gamma-aminobutyric acid (GABA)-dependent 36Cl- uptake indicated that the pyrolysis product of liquid trimethylol propane (TMP) containing organic phosphates interacts with the GABA/benzodiazepine receptor chloride ionophore complex (GBRC) producing a receptor-mediated reduction in 36Cl- flux. The pyrolysate-ligand interaction was competitive and directly proportional to the trimethylol propane phosphate (TMPP) content of the combustion product. TBPS displacement demonstrated that TMPP had less affinity than did TBPS and picrotoxin, but greater affinity than GABA, racemic dimethylbutyl barbituric acid (DMBB), clonazepam, and phenobarbital for their respective recognition sites. Addition of exogenous GABA was a necessary condition for demonstrating clonazepam-induced ligand displacement, thus being indicative of an allosteric interaction. The same rank order held for altering GABA-dependent 36Cl- uptake with the caveat of inhibitors vs enhancers, and noting that pentobarbital was less potent than DMBB. Concentration-dependent ligand displacement by GBRC agonists and antagonists quantitatively correlated with alterations in GABA-dependent 36Cl- uptake. The median convulsant dose (CD50) of pyrolysate TMPP was higher than that of synthetic TMPP. The presence of combustion by-products altering the dispositional kinetics of the former is felt to be the reason for this difference. Under our experimental conditions, phenobarbital was the most effective antidote for pyrolysate (TMPP) toxicity. The inhalant convulsant, flurothyl, was found not to displace [35S]TBPS binding, not to affect GABA-dependent 36Cl- uptake, and not to respond to the anticonvulsants in a manner consistent with a strict GABAA receptor phenomenon.

Animals↗
PubMed1991

Cell behaviour on polymer surfaces grafted with non-ionic and ionic monomers.

Following exposure to corona discharge, a polyethylene film was graft polymerized with different water-soluble monomers such as acrylamide (non-ionic), acrylic acid (anionic), 2-acrylamide-2-methyl propane sulphonic acid (anionic), styrene sulphonic acid sodium salt (anionic) and N,N-dimethylaminopropyl acrylamide (cationic). Attachment and proliferation of HeLa S3 cells were studied for grafted surfaces with different zeta potentials and contact angles. The polyethylene surface graft polymerized with styrene sulphonic acid sodium salt exhibited high cell attachment and protein adsorption, whereas the cells did not adhere to the 2-acrylamide-2-methyl propane sulphonic acid graft-polymerized surface, although both surfaces had high negative zeta potentials. Graft polymerization of acrylamide reduced the zeta potential of surface close to zero and rejected the cell attachment. The polyethylene surface became highly cell-adhesive through graft polymerization of the cationic N,N-dimethylaminopropyl acrylamide monomer, but too much grafting killed the attaching cells. Once the cells attached to a surface without being killed, they could proliferate at the same growth rate, whatever their surface zeta potential.

Acrylic Resins↗
PubMed1993

Osteoblast-like cell (MC3T3-E1) proliferation on bioerodible polymers: an approach towards the development of a bone-bioerodible polymer composite material.

An osteogenic cell line (MC3T3-E1) was used to study the potential of bioerodible polymers and ceramics to support osteoblast growth for a proposed bone-polymer composite for skeletal tissue repair. MC3T3-E1 cells were seeded on to 50:50 poly(lactide-co-glycolide), hydroxyapatite, 50:50 hydroxyapatite/poly(lactide-co-glycolide), and the poly(anhydride), poly(bis(p-carboxyphenoxy) propane surfaces. Cell attachment and growth on these surfaces was found to be highest on poly(lactide-co-glycolide), the least on hydroxyapatite and hydroxyapatite/poly(lactide-co-glycolide) combinations gave intermediate values. The order of adhesion and growth of MC3T3-E1 cells on the polymer and ceramic systems was poly(lactide-co-glycolide) is greater than hydroxyapatite/poly(lactide-co-glycolide) which is greater than hydroxyapatite. Negligible growth was found on poly(bis(p-carboxyphenoxy) propane. High alkaline phosphatase activity for the cells grown on poly(lactide-co-glycolide) and hydroxyapatite/poly(lactide-co-glycolide) confirmed retention of the osteoblast phenotype. This in vitro evaluation suggests that poly(lactide-co-glycolide) and hydroxyapatite/poly(lactide-co-glycolide) combinations may be candidate biomaterials for the construction of a cell-polymer matrix for skeletal tissue regeneration.

Alkaline Phosphatase↗
PubMed1984

Metabolism of anethole. I. Pathways of metabolism in the rat and mouse.

The metabolic fate of the naturally occurring food flavouring trans-anethole has been investigated in rats and mice. A single 50-mg/kg dose of trans-[methoxy-14C]anethole was given orally to female Wistar albino rats and by ip injection to male CD-1 mice. The major routes of elimination of 14C were the urine and expired air (as 14CO2). Excretion of 14C in the faeces and as volatile compounds in the expired air was very low (total less than 2% of the dose). Urinary metabolites were separated by solvent extraction, TLC and HPLC and were characterized by MS and GC-MS directly and following methylation or trimethylsilylation, the results being compared where possible with authentic standards. Eleven 14C-containing urinary metabolites were identified in the rat and ten in the mouse. These compounds arose from side-chain oxidation, side-chain cleavage and various conjugations. The major urinary metabolites were two isomers of 1-(4'-methoxyphenyl)propane-1,2-diol, 2-hydroxy-1-methylthio-1-(4'-methoxyphenyl)propane and 4-methoxyhippuric acid, the first three all being excreted as glucuronides. In addition to these 14C-labelled metabolites, 4-hydroxypropenylbenzene, the unlabelled product of oxidative O-demethylation of trans-[14C]anethole, was excreted extensively in urine as the glucuronide.

Allylbenzene Derivatives↗
PubMed1991

Aldehyde dismutation catalyzed by pulmonary carbonyl reductase: kinetic studies of chloral hydrate metabolism to trichloroacetic acid and trichloroethanol.

The kinetics of the NAD(P)(+)-linked aldehyde dismutation by pulmonary carbonyl reductase of guinea pig were studied using a highly hydrated substrate, chloral hydrate (CH). The enzyme irreversibly converted the substrate into trichloroacetic acid (TCA) and trichloroethanol (TCE) in the presence of the reduced or oxidized cofactors, of which NAD(P)+ gave a higher reaction rate than did NAD(P)H, and the concentration ratios of the two products (TCA plus TCE) to CH utilized were 1:1. In the NAD(P)(+)-linked reaction TCA was the predominant product and its amount was compatible with that of TCE plus NAD(P)H produced, whereas in the NAD(P)H-linked reaction equal amounts of TCA and TCE were formed and the cofactor was little oxidized. These results suggest that the enzyme oxidized the hydrated aldehydes to TCA with NAD(P)+ as the cofactor and reduced the unhydrated aldehyde to TCE with NAD(P)H. The steady-state kinetic measurements in the NADP(+)-linked CH oxidation were consistent with an ordered Bi Bi mechanism which is the same as that for the secondary alcohol oxidation by the enzyme. The dehydrogenase activity was inhibited competitively with respect to CH by a secondary alcohol substrate, propan-2-ol. The CH and propan-2-ol dehydrogenase activities were similarly inactivated by 2,4,6-trinitrobenzene-sulfonate, and NADP(H), several cofactor analogs and a cofactor-competitive inhibitor, Cibacron blue dye, protected against the inactivation, which suggest that lysine residues are essential for catalysis.

Alcohol Oxidoreductases↗
PubMed1992

Long-lived fluorescence lifetime from tyrosine in a peptide derived from S-100b.

It was shown in an earlier report (Turner et al., 1989, Biochem. Cell Biol. 67; 179-186) that the anomalous steady-state fluorescence emission spectra observed for the protein S-100b in aqueous solution at pH 7.5 contains a long-lived fluorescence decay component. In this study, a peptide consisting of residues 11 to 27 of the beta-subunit, was investigated. 11Ile-Asp-Val-Phe-His15-Gln-Tyr-Ser-Gly-Arg20-Glu-Gly- Asp-Lys-His25-Lys-Leu27 Fluorescence lifetimes were measured at the emission maximum and in the red edge of the spectrum. At wavelengths greater than 320 nm, the data was best fit with three exponentials. The third exponential gave lifetimes of 13.1 ns and 15.9 ns when the peptide was dissolved in the solvents propane-2-ol and propane-1,2-diol, respectively (lambda EX = 275 nm, lambda EM = 350 nm). These fluorescence lifetimes are similar to that observed for a decay component of native S-100b in the red edge of the emission, suggesting that the 1 degrees and 2 degrees features of a heptadecapeptide from S-100b protein has enough structural information when dissolved in solvents of intermediate polarity provide appropriate conditions for long-lived fluorescence from a tyrosine/tyrosinate species to occur.

Amino Acid Sequence↗
PubMed1991

Study of human urinary metabolism of fenfluramine using gas chromatography-mass spectrometry.

The metabolism of (+/-)fenfluramine, 1-(m-trifluoromethylphenyl)-2-N-ethylpropane, an anoretic agent, was investigated in humans. The analysis method was based on the use of ion-exchange resin extraction, solid-phase purification on the Bond Elut1M C8 cartridge, gradient elution high-performance liquid chromatography, enzymic hydrolysis of conjugates, further purification by Bond Elut C8 cartridge, derivatisation and capillary column gas chromatography-mass spectrometry (GC-MS). After administration of a 1 mg kg-1 oral dose, four metabolites plus unchanged fenfluramine were recovered in the 0-24 h urine from human volunteers and characterised by GC-MS. In the conjugated form, fenfluramine, norfenfluramine and m-trifluoromethylhippuric acid were detected by GC-MS. In the aglycone form, the major metabolite, 1-(m-trifluoromethylphenyl)-1,2-propane diol (fenfluramine diol), was monitored using GC-MS. The mass spectral characteristics of the m-trifluoromethylhippuric acid methyl ester, 1-(m-trifluoromethylphenyl)-1,2-propane ditrifluoracetate derivatives and the norfenfluramine and fenfluramine free base obtained under electron-impact ionization are presented. The metabolism of fenfluramine is discussed including a metabolic pathway in man accounting for the formation of its biotransformation products.

Biotransformation↗
PubMed1993

Vasodilatory and toxic effects of spin traps on aerobic cardiac function.

The objective of this study was to compare the effect of several structurally related nitrone and nitroso spin traps on the function of the isolated bicarbonate-buffer perfused rat heart model. Spin traps investigated were alpha-phenyl-tert-butyl N-nitrone (PBN), alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone (POBN), 2-methyl-2-nitroso propane (MNP), 2-hydroxymethyl-2-nitroso propane (MNP/OH), nitrosobenzene (NB), dibromonitrosobenzene-sulfonic acid (DBNBS), and 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO). During perfusion of hearts with increasing concentrations of spin traps, ventricular pressure, coronary flow rate, and heart rate were continuously recorded. The extent of contractile recovery was subsequently measured upon return to spin-trap free perfusion. The percentage of maximum increase in coronary flow with PBN, POBN, MNP, MNP-OH, NB, DBNBS, and DMPO were 11, 40, 45, 66, 28, 28, and 29%, respectively. Thus, all nitroso and nitrone spin traps studied acted as vasodilators. Over the dose range studied, POBN, MNP, MNP/OH, and DMPO did not exert any chronotropic effect. PBN, NB, and DBNBS exerted a negative chronotropic effect at higher concentrations. All spin traps studied, with the exception of DMPO, exerted a negative inotropic effect at the higher concentrations studied. We conclude that all spin traps examined acted as coronary vasodilators. Their negative chronotropic and inotropic effects were minimal in comparison and only manifest at the higher concentrations studied.

Aerobiosis↗
PubMed2004

Effect of composite resin biodegradation products on oral streptococcal growth.

Hydrolytic degradation by-products associated with the constitutive monomers 2,2-bis [4-(2-hydroxy-3-methacryloxypropoxy) phenyl] propane (bis-GMA), bisphenol A polyethylene glycol diether dimethacrylate (bis-EMA), and triethylene glycol dimethacrylate (TEDGMA) used in dental restorative composites include bis-hydroxy-propoxyphenyl propane (bis-HPPP), ethoxylated bisphenol A (E-bisPA), methacrylic acid (MA), and triethylene glycol (TEG). These products are generated from the interaction of human salivary esterases with the composites. Recent findings have indicated that TEGDMA has the ability to modulate oral bacteria but it is unclear which components of TEGDMA are related to the observed effects. The objective of the current study was to investigate the influence of TEGDMA derived degradation products MA and TEG on the growth of three strains of oral bacteria: S. mutans strains NG8 and JH1005, and S. salivarius AT2. Bacterial growth rates were measured at 37 degrees C, and pH values of 5.5 (representative of cariogenic state) or 7.0 at concentrations of 0-50mmol/l for MA (Sigma, US) and 0-100mmol/l for TEG (Sigma, US). It was found that at pH 5.5 TEG significantly stimulated the growth of both S. mutans strains ( p<0.05 ) in the concentration range of 0.5-10.0mmol/l and stimulated the growth of S. salivarius AT2 for the entire concentration range tested (p<0.05). TEG (above 50mmol/1) did not significantly affect the doubling times of S. salivarius at pH of 7.0 and it inhibited the growth of both S. mutans strains above 50mmol/l at the same pH value. At pH 5.5 MA inhibited the growth of all three strains with increasing concentration. At neutral pH, the growth of S. mutans NG8 strain was significantly reduced by MA ( p<0.05 ) above 10mmol/l. In summary, these results indicate that TEG and MA modulate the growth rate of important oral bacteria in a concentration and pH dependent manner.

Biodegradation, Environmental↗
PubMed2005

Biomechanical properties of high-toughness double network hydrogels.

This study evaluated the wear property of four novel double-network (DN) hydrogels, which was composed of two kinds of hydrophilic polymers, using pin-on-flat wear testing. The gels involve PAMPS-PAAm gel which consists of poly(2-acrylamide-2-metyl-propane sulfonic acid) and polyacrylamide, PAMPS-PDAAAm gel which consists of poly(2-acrylamide-2-metyl-propane sulfonic acid) and poly(N,N'-dimetyl acrylamide), Cellulose/PDMAAm gel which consists of bacterial Cellulose and poly dimetyl-acrylamide, and Cellulose-Gelatin gel which consists of bacterial Cellulose and Gelatin. Ultra-high molecular weight polyethylene (UHMWPE) was used as a control of a clinically available material. Using a reciprocating apparatus, 10(6) cycles of friction between a flat specimen and ceramic pin were repeated in water under a contact pressure of 0.1 MPa. To determine the depth and the roughness of the concave lesion created by wear, a confocal laser microscope was used. As a result, the maximum wear depth of the PAMPS-PDMAAm gel (3.20 microm) was minimal in the five materials, while there was no significant difference compared to UHMWPE. There were significant differences between UHMWPE and one of the other three gels. The PAMPS-PAAm gel (9.50 microm), the Cellulose-PDMAAm gel (7.80 microm), and the Cellulose-Gelatin gel (1302.40 microm). This study demonstrated that the PAMPS-PDMAAm DN gel has an amazing wear property as a hydrogel that is comparable to the UHMWPE. In addition, the PAMPS-PAAm and Cellulose-PDMAAm DN gels are also resistant to wear to greater degrees than conventionally reported hydrogels. On the other hand, this study showed that the Cellulose-Gelatin DN gel was not resistant to wear.

Acrylic Resins↗
PubMed2005

A new method for quantifying the intensity of the C=C band of dimethacrylate dental monomers in their FTIR and Raman spectra.

The degree of conversion (DC) of methacrylate dental resins is typically determined by spectroscopically measuring the decrease of the vinyl (C=C) stretching band at 1640 cm(-1), ratioed before and after polymerization to an internal standard (aromatic ring quadrant stretching vibration (Ph)) at around 1609 cm(-1). While standard methods exist for measuring the intensity of the C=C and Ph peaks from the FTIR or Raman spectrum, these methods either fail under certain circumstances, or lack a physical basis, being purely based on spectral features. In this study, we present a rigorous method (named rotational isomerism method) for determining the intensity of the vinyl and aromatic bands from the FTIR and Raman spectra of dental monomer mixtures, and compare it to a standard baseline method (SBM) and a standard curve fitting method. Model triethyleneglycol dimethacrylate (TEGDMA)/2,2-bis(4-hydroxyphenyl)propane (Bisphenol-A) and TEGDMA/2,2-bis(4-(2-hydroxy-3-methacryloxypropoxy)phenyl)propane (Bis-GMA) mixtures with a series of known C=C/Ph molar ratios were prepared in order to simulate the effect of curing. The accuracy of the new method for measuring the DC was found to be as good as the commonly used SBM. The standard curve fitting method was shown to be inappropriate for measuring C=C/Ph ratios by FTIR spectroscopy due to its inability to realistically simulate the features of the spectra. The insight gained through the use of this new method may be useful for the characterization of other methacrylate biomaterials.

Benzhydryl Compounds↗
PubMed2005

Discovery of non-carbohydrate inhibitors of aminoglycoside-modifying enzymes.

Chemical modification and inactivation of aminoglycosides by many different enzymes expressed in pathogenic bacteria are the main mechanisms of bacterial resistance to these antibiotics. In this work, we designed inhibitors that contain the 1,3-diamine pharmacophore shared by all aminoglycoside antibiotics that contain the 2-deoxystreptamine ring. A discovery library of molecules was prepared by attaching different side chains to both sides of the 1,3-diamine motif. Several of these diamines showed inhibitory activity toward two or three different representative aminoglycoside-modifying enzymes (AGMEs). These studies yielded the first non-carbohydrate inhibitor N-cyclohexyl-N'-(3-dimethylamino-propyl)-propane-1,3-diamine (Compound G,H) that is competitive with respect to the aminoglycoside binding to the enzyme aminoglycoside-2''-nucleotidyltransferase-Ia (ANT2''). Another diamine molecule N-[2-(3,4-dimethoxyphenyl)-ethyl]-N'-(3-dimethylamino-propyl)-propane-1,3-diamine (Compound H,I) was shown to be a competitive inhibitor of two separate enzymes (aminoglycoside-3'-phosphotransferase-IIIa (APH3') and ANT2'') with respect to metal-ATP. Thermodynamic and structural-binding properties of the complexes of APH3' with substrates and inhibitor were shown to be similar to each other, as determined by isothermal titration calorimetry and NMR spectroscopy.

Aminoglycosides↗