Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GLUTARATES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed2004

3-hydroxyglutaric acid enhances glutamate uptake into astrocytes from cerebral cortex of young rats.

A predominantly neurological presentation is common in patients with glutaric acidemia type I (GA-I). 3-hydroxyglutaric acid (3-OHGA), which accumulates in affected patients, has recently been demonstrated to play a central role in the neuropathogenesis of this disease. In the present study, we investigated the in vitro effects of 3-OHGA at concentrations ranging from 10 to 1000 microM on various parameters of the glutamatergic system, such as the basal and potassium-induced release of [3H]glutamate by synaptosomes, as well as on Na+-dependent [3H]glutamate uptake by synaptosomes and astrocytes and Na+-independent [3H]glutamate uptake by synaptic vesicles from cerebral cortex of 30-day-old Wistar rats. First, we observed that exposure of cultured astrocytes to 3-OHGA for 20 h did not reduce their viability. Furthermore, 3-OHGA significantly increased Na+-dependent [3H]glutamate uptake by astrocytes by up to 80% in a dose-dependent manner at doses as low as 30 microM. This effect was not dependent on the presence of the metabolite during the uptake assay, since it occurred even when 3-OHGA was withdrawn from the medium after cultured cells had been exposed to the acid for approximately 1 h. All other parameters investigated were not influenced by this organic acid, indicating a selective action of 3-OHGA on astrocyte transporters. Although the exact mechanisms involved in 3-OHGA-stimulatory effect on astrocyte glutamate uptake are unknown, the present findings contribute to the understanding of the pathophysiology of GA-I, suggesting that astrocytes may protect neurons against excitotoxic damage caused by 3-OHGA by increasing glutamate uptake and therefore reducing the concentration of this excitatory neurotransmitter in the synaptic cleft.

Animals↗
PubMed2003

Late-onset form of beta-electron transfer flavoprotein deficiency.

Multiple acyl-CoA-dehydrogenase deficiency (MADD) or glutaric aciduria type II (GAII) are a group of metabolic disorders due to deficiency of either electron transfer flavoprotein (ETF) or electron transfer flavoprotein ubiquinone oxidoreductase (ETF-QO). We report the clinical features and biochemical and molecular genetic analyses of a patient with a mild late-onset form of GAII due to beta-ETF deficiency. Biochemical data showed an abnormal urine organic acid profile, low levels of free carnitine, increased levels of C(10:1n-6), and C(14:1n-9) in plasma, and decreased oxidation of [9,10-3H]palmitate and [9,10-3H]myristate in fibroblasts, suggesting MAD deficiency. In agreement with these findings, mutational analysis of the ETF/ETFDH genes demonstrated an ETFB missense mutation 124T>C in exon 2 leading to replacement of cysteine-42 with arginine (C42R), and a 604_606AAG deletion in exon 6 in the ETFB gene resulting in the deletion of lysine-202 (K202del). The present report delineates further the phenotype of mild beta-ETF deficiency and illustrates that the differential diagnosis of GAII is readily achieved by mutational analysis.

Amino Acid Metabolism, Inborn Errors↗
PubMed2001

Isotope-tagged cross-linking reagents. A new tool in mass spectrometric protein interaction analysis.

In protein interaction analysis, one promising method to identify the involved proteins and to characterize interacting sites at the same time is the mass spectrometric analysis of enzymatic hydrolysates of covalently cross-linked complexes. While protein identification can be accomplished by the methodology developed for proteome analysis, the unequivocal detection and characterization of cross-linked sites remained involved without selection criteria for linked peptides in addition to mass. To provide such criteria, we incorporated cross-links with a distinct isotope pattern into the microtubule-destabilizing protein Op18/stathmin (Op18) and into complexes formed by Op18 with tubulin. The deuterium-labeled cross-linking reagents bis(sulfosuccinimidyl)-glutarate-d4, -pimelate-d4, and -sebacate-d4 were prepared together with their undeuterated counterparts and applied as a 1:1 mixture of the respective d0 and d4 isotopomers. The resulting d0/d4 isotope tags allowed a straightforward mass spectrometric detection of peptides carrying the linker even in complex enzymatic protein hydrolysates. In the structure elucidation of the linked peptides by MS/MS, the assignment of the linked amino acids was again greatly facilitated by the d0/d4 tag. By applying two cross-linkers with similar reactivity but different spacer length in parallel, even doublets with very low intensity could be assigned with high confidence in MS and MS/MS spectra. Since in the Op18-tubulin complexes only a limited number of peptides carried the linker, the identification of the involved proteins per se was not impeded, thus accomplishing both protein identification and characterization of interacting sites in the same experiment. This novel methodology allowed us to significantly refine the current view of the complex between Op18 and tubulin corroborating the tubulin "capping" activity of the N-terminal domain of Op18.

Amino Acid Sequence↗
PubMed2003

Investigation of surface changes of nanoparticles using TM-AFM phase imaging.

Tapping-mode AFM (TM-AFM) phase imaging was utilized to characterize the surface changes of nanosize particles, in regard to the effects of different amounts of condensed water and organic coatings on particle surfaces. Model nanoparticles were continuously examined under various relative humidity (RH) levels by concurrently obtaining both topographic and phase images. The condensed water appeared to soften particle surfaces and to increase tip-sample attractive interaction over relatively stiff surfaces, which were shown with dark phase contrasts and negative phase shift values in phase images. Under high RH, a massive amount of water gave the particles a droplet-like surface, which reversed the original negative phase shifts to positive values with bright contrasts. Glutaric-acid coatings provided a compliant surface with high viscosity resulting in a dark phase contrast, whereas water droplets containing relatively low viscosity gave a bright phase contrast and positive phase shift. Overall, our results show that it is essential to describe the physical properties of a sample surface as solid, soft, or droplet-like material in order to derive a meaningful understanding of the surface changes of nanosize particles based on TM-AFM phase images. In contrast to other phase imaging studies, this work clearly correlates continuous surface changes with phase images, demonstrating a promising approach to characterize environmental nanoparticles.

Dicarboxylic Acids↗
PubMed2003

Studies into the thermodynamic origin of negative cooperativity in ion-pairing molecular recognition.

The association of synthetic receptors to target guests often proceeds through the cooperative action of multiple binding forces. An investigation into the thermodynamic origin of cooperativity in ion-pairing host-guest binding in water is described. The binding affinities of 1,2,3,4-butanetetracarboxylate, tricarballate, glutarate, and acetate to a C(3)(v) symmetric metallo-host (1) are characterized in terms of the binding constants (K(a)) and the thermodynamic parameters deltaG degrees, deltaH degrees, and deltaS degrees, as determined by isothermal titration calorimetry (ITC). These values are used to determine the individual contributions of the binding interaction to the overall binding. Several ways to view the combination of the individual binding events that make up the whole are analyzed, all of which lead to the conclusion of negative cooperativity. Combined, the data were used to evaluate the thermodynamic origin of negative cooperativity for this series of guests, revealing that entropy is the largest contributing factor. An interpretation of this result focuses upon differences in the number of water molecules displaced upon binding.

Acetic Acid↗
PubMed2002

Nanomolar small molecule inhibitors for alphav(beta)6, alphav(beta)5, and alphav(beta)3 integrins.

Integrin adhesion receptors frequently recognize a core amino acid sequence, Arg-Gly-Asp, in their target ligands. Inhibitors with the ability to inhibit one or a small subset of such RGD-dependent integrins have been invaluable in defining their biological function. Here, we have characterized low molecular weight inhibitors for their ability to specifically inhibit alphav(beta)6 integrin, a fibronectin/tenascin receptor. As of yet, no nonpeptidic inhibitor of alphav(beta)6 was known. New peptidomimetic and nonpeptidic compounds were examined in isolated integrin binding assays and in cell adhesion assays for their ability to block alphav(beta)6, alphav(beta)3, alphav(beta)5, and alphalIb(beta)3 integrins. The compounds are based on an aromatically substituted beta amino acid or glutaric acid derivative as an acidic center and an aminopyridyl or guanidyl residue as a basic mimetic. We found several classes of inhibitors with different selectivities, especially mono- or biselectivity on the alpha(v)-integrins alphav(beta)6 and alphav(beta)3, and nanomolar activity. Furthermore, nearly all compounds are inactive on alphaIIb(beta)3. Compound 11 is the first specific, peptidomimetic inhibitor of the alphav(beta)6 integrin receptor.

Amino Acids↗
PubMed2002

Synthesis, pharmacokinetics, efficacy, and rat retinal toxicity of a novel mitomycin C-triamcinolone acetonide conjugate.

A novel conjugate of mitomycin C (MMC) and triamcinolone acetonide (TA) was synthesized using glutaric acid as a linker molecule. To determine the rate of hydrolysis, the conjugate was dissolved in aqueous solution and the rate of appearance of free MMC and TA was determined by high-performance liquid chromatography analysis. Antiproliferative activity of the MMC-TA conjugate and parent compounds was assessed using an NIH 3T3 fibroblast cell line. Cell growth was quantified using the MTT assay. Kinetic analysis of the hydrolysis rate demonstrated that the conjugate had a half-life of 23.6 h in aqueous solutions. The antiproliferative activities of the MMC-TA conjugate and MMC were both concentration dependent, with similar IC(50) values of 2.4 and 1.7 microM, respectively. However, individual responses at concentrations above 3 microM showed that the conjugate was less active than MMC alone. TA alone showed only limited inhibition of cell growth. Studies evaluating intravitreal injection of the conjugate demonstrate that this agent produced no measurable toxicity. Our data provide evidence that the MMC-TA conjugate could be used as a slow-release drug delivery system. This could in turn be used to modulate a posttreatment wound healing process or to treat various proliferative diseases.

3T3 Cells↗
PubMed2004

Animal models for glutaryl-CoA dehydrogenase deficiency.

In vitro studies suggest that excitotoxic cell damage is an underlying mechanism for the acute striatal damage in glutaryl-CoA dehydrogenase (GCDH) deficiency. It is believed to result from an imbalance of glutamatergic and GABAergic neurotransmission induced by the accumulating organic acids 3-hydroxyglutaric acid (3-OH-GA) and to a lesser extent glutaric acid (GA). Stereotaxic administration of 3-OH-GA and GA into the rat striatum have confirmed these results, but may not truly represent the effect of chronic exposure to these compounds. In an attempt to better understand the pathophysiology of GCDH deficiency in vivo , two animal models have been utilized. A mouse that lacks GCDH activity in all tissues was generated by gene targeting in embryonic stem cells. These animals develop the characteristic biochemical phenotype of the human disease. Pathologically, these mice have a diffuse spongiform myelinopathy similar to that in human patients; however, there is no evidence for acute striatal damage or sensitivity to acute encephalopathy induced by catabolism or inflammatory cytokines. A naturally occurring animal model, the fruit-eating bat Rousettus aegypticus, lacks hepatic and renal GCDH activity, but retains cerebral enzyme activity. Like the mouse, these bats develop the characteristic biochemical phenotype of glutaryl-CoA dehydrogenase deficiency, but lack overt neurological symptoms such as dystonia. It is not known whether they also develop the spongiform myelinopathy seen in the Gcdh-deficient mice. Otherwise, these constellations would suggest that cerebral GCDH deficiency is responsible for the development of neuronal damage. The lack of striatal damage in these two rodent models may also be related to species differences. However, they also highlight our lack of a comprehensive understanding of additional factors that might modulate the susceptibiliy of neurons to accumulating 3-OH-GA and GA in GCDH deficiency. Unravelling these mechanisms may be the key to understanding the pathophysiology of this unique disease and to the development of neuroprotective strategies.

Amino Acid Metabolism, Inborn Errors↗
PubMed2004

Challenges for basic research in glutaryl-CoA dehydrogenase deficiency.

During the last decades, efforts have been made to elucidate the complex mechanisms underlying neuronal damage in glutaryl-CoA dehydrogenase deficiency. A combination of in vitro and in vivo investigations have facilitated the development of several hypotheses, including the probable pathogenic role of accumulating glutaric acid and 3-hydroxyglutaric acid. However, there are still many shortcomings that limit an evidence-based approach to treating this inborn error of metabolism. Major future goals should include generation of a suitable animal model for acute striatal necrosis, investigation of the formation, distribution and exact intra- and extracellular concentrations of accumulating metabolites, a deeper understanding of striatal vulnerability, and systematic investigation of effects on cerebral gene expression during development and of the modulatory role of inflammatory cytokines.

Amino Acid Metabolism, Inborn Errors↗
PubMed1970

Differential long-term effects of D-chloramphenicol on the biogenesis of mitochondria in normal and regenerating rat liver.

1. Normal and partially hepatectomized rats (150g) were injected daily with d-chloramphenicol (20mg) for a period of 4 weeks, in order to investigate whether defective mitochondria could be induced in vivo in higher organisms as in yeast, and to measure the degree of inhibition of the mitochondrial function thus obtained. 2. The antibiotic did not affect growth and increased the amount of liver protein without changing the mitochondrial yield. 3. The respiration of isolated mitochondria from regenerated liver (regeneration completed) with succinate, alpha-oxo-glutarate, isocitrate and malate, was decreased in the chloramphenicol-treated rats, whereas in normal liver the antibiotic increased the mitochondrial oxygen consumption with succinate and did not significantly change the respiration with other substrates. 4. Mitochondrial cytochromes and respiratory enzymes were also decreased in amount in regenerated liver from the treated rats and enhanced in normal liver. 5. The protein specific radioactivities of most mitochondrial and microsomal subfractions, 30min after an injection of [(14)C]leucine, were decreased in regenerated liver under the action of chloramphenicol. Conversely, the incorporation of [(14)C]leucine into proteins of most subfractions in incubations of liver slices was enhanced in the case of normal rats treated with the antibiotic. 6. It is concluded that in regenerated liver chloramphenicol induces functionally defective mitochondria by inhibiting their biogenesis, whereas in normal liver the stimulation of respiration and protein synthesis is probably a secondary detoxication response.

Animals↗
PubMed1971

The effect of salts on catecholamine fluxes and adenosine triphosphatase activity in storage vesicles from the adrenal medulla.

1. Influx and efflux of catecholamine and adenosine triphosphatase activity in storage vesicles from the adrenal medulla were studied with dl-[(14)C]adrenaline in different media. 2. The lowest values for flux and adenosine triphosphatase activity were observed in sucrose media in which an ATP-dependent influx of catecholamine compensated for an efflux of the same magnitude. Efflux in the presence or absence of ATP was similar. 3. In media containing sodium succinate or glutarate adenosine triphosphatase activity was higher and the ATP-dependent influx of catecholamine was about twice that observed in iso-osmotic sucrose medium. In the presence of ATP influx and efflux of catecholamine were balanced; in its absence there was a net release of catecholamine, since efflux was more than twice the influx. Efflux in the presence or absence of ATP was similar. 4. In media containing sodium or potassium chloride and in the presence of ATP influx and adenosine triphosphatase activity were further enhanced, but in the absence of ATP there was no further increase in influx, since catecholamine was released with or without ATP at the same rate. Efflux was therefore twice as high in the presence of ATP as in its absence. 5. Sodium nitrate suppressed the ATP-dependent influx nearly completely, but caused a greatly enhanced efflux, which was twice as high in the presence of ATP as in its absence. 6. The extinction of vesicular suspensions remained unchanged in the presence of ATP under conditions where the catecholamine efflux was balanced by the influx. Under conditions where the efflux was not compensated by influx, the extinction of the suspensions decreased in the presence of ATP more than in its absence.

Adenosine Triphosphatases↗
PubMed1994

Control of glucokinase translocation in rat hepatocytes by sorbitol and the cytosolic redox state.

In rat hepatocytes cultured in 5 mM glucose, glucokinase activity is present predominantly in a bound state, and during permeabilization of the cells with digitonin in the presence of Mg2+ less than 20% of glucokinase activity is released. However, incubation of hepatocytes with a higher [glucose] [concn. giving half-maximal activation (A50) 15 mM] or with fructose (A50 50 microM) causes translocation of glucokinase from its Mg(2+)-dependent binding site to an alternative site [Agius and Peak (1993) Biochem. J. 296, 785-796]. A comparison of various substrates showed that sorbitol (A50 8 microM) was 6-fold more potent than fructose at causing glucokinase translocation, whereas tagatose was as potent and mannitol was > 10-fold less potent (A50 550 microM). These substrates also stimulate glucose conversion into glycogen with a similar relative potency, suggesting that conversion of glucose into glycogen is dependent on the binding and/or location of glucokinase within the hepatocyte. Ethanol and glycerol inhibited the effects of fructose, sorbitol and glucose on glucokinase translocation, whereas dihydroxy-acetone had a small additive effect at sub-maximal substrate stimulation. The converse effects of glycerol and dihydroxy-acetone suggest a role for the cytosolic NADH/NAD+ redox state in controlling glucokinase translocation. Titrations with three competitive inhibitors of glucokinase did not provide evidence for involvement of glucokinase flux in glucose-induced glucokinase translocation: N-acetylglucosamine inhibited glucose conversion into glycogen, but not glucose-induced glucokinase translocation; glucosamine partially suppressed glucose-induced and fructose-induced glucokinase translocation, at concentrations that caused total inhibition of glucose conversion into glycogen; D-mannoheptulose increased glucokinase release and had an additive effect with glucose. 3,3'-Tetramethylene-glutaric acid (5 mM), an inhibitor of aldose reductase, inhibited glucokinase translocation induced by glucose, but not that by sorbitol or fructose, suggesting that glucose may induce glucokinase translocation by conversion into sorbitol. Sorbitol generated from glucose intrahepatically or extrahepatically in hyperglycaemic conditions may be a physiological regulator of hepatic glucokinase translocation.

Animals↗
PubMed2001

The function of Arg-94 in the oxidation and decarboxylation of glutaryl-CoA by human glutaryl-CoA dehydrogenase.

Glutaryl-CoA dehydrogenase catalyzes the oxidation and decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2). Inherited defects in the protein cause glutaric acidemia type I, a fatal neurologic disease. Glutaryl-CoA dehydrogenase is the only member of the acyl-CoA dehydrogenase family with a cationic residue, Arg-94, situated in the binding site of the acyl moiety of the substrate. Crystallographic investigations suggest that Arg-94 is within hydrogen bonding distance of the gamma-carboxylate of glutaryl-CoA. Substitution of Arg-94 by glycine, a disease-causing mutation, and by glutamine, which is sterically more closely related to arginine, reduced k(cat) of the mutant dehydrogenases to 2-3% of k(cat) of the wild type enzyme. K(m) of these mutant dehydrogenases for glutaryl-CoA increases 10- to 16-fold. The steady-state kinetic constants of alternative substrates, hexanoyl-CoA and glutaramyl-CoA, which are not decarboxylated, are modestly affected by the mutations. The latter changes are probably due to steric and polar effects. The dissociation constants of the non-oxidizable substrate analogs, 3-thiaglutaryl-CoA and acetoacetyl-CoA, are not altered by the mutations. However, abstraction of a alpha-proton from 3-thiaglutaryl-CoA, to yield a charge transfer complex with the oxidized flavin, is severely limited. In contrast, abstraction of the alpha-proton of acetoacetyl-CoA by Arg-94 --> Gln mutant dehydrogenase is unaffected, and the resulting enolate forms a charge transfer complex with the oxidized flavin. These experiments indicate that Arg-94 does not make a major contribution to glutaryl-CoA binding. However, the electric field of Arg-94 may stabilize the dianions resulting from abstraction of the alpha-proton of glutaryl-CoA and 3-thiaglutaryl-CoA, both of which contain gamma-carboxylates. It is also possible that Arg-94 may orient glutaryl-CoA and 3-thiaglutaryl-CoA for abstraction of an alpha-proton.

Acyl Coenzyme A↗
PubMed2005

Isolation and functional characterization of a novel organic solute carrier protein, hOSCP1.

We succeeded in isolating a novel organic solute carrier from a human placenta cDNA library. The isolated cDNA consisted of 1137 base pairs that encoded a 379-amino acid protein, hOSCP1. Northern blot and reverse transcription PCR analyses revealed that the hOSCP1 mRNA is expressed in the placenta and testis and weakly expressed in the thymus and small intestine. When expressed in Xenopus laevis oocytes, hOSCP1 mediated the high affinity transport of p-aminohippurate (PAH) (K(m) = 35.0 +/- 7.5 microm) and tetraethylammonium (K(m) = 62.3 +/- 12.2 microm) in a sodium-independent manner. However, the hOSCP1-expressing oocyte did not mediate the transport of L-carnitine. The transport of PAH by hOSCP1 was sensitive to pH, but the tetraethylammonium was not transported at the high pH examined. hOSCP1 transported prostaglandin E(2), prostaglandin F(2alpha), estrone sulfate, glutarate, L-leucine, L-ascorbic acid, and tetracycline. Thus, hOSCP1 also showed broad substrate specificity. A wide range of structurally unrelated organic compounds inhibited the hOSCP1-mediated PAH uptake. Immunohistochemical analysis revealed that the hOSCP1 protein is localized in the basal membrane of the syncytiotrophoblast in the human placenta. Our results suggest that hOSCP1 is a novel polyspecific organic solute carrier protein responsible for drug clearance from the human placenta.

Amino Acid Sequence↗
PubMed2001

The effect of surfactants on the deliquescence of sodium chloride.

This study investigated the deliquescence of sodium chloride aerosol with surfactants at a retention time of 4.24 sec. Two surfactants used in this study, glutaric acid and pyruvic acid, are found in atmospheric aerosol and have a high hydrophile-lipophile balance (HLB) value. The experimental system consisted of a relative humidity conditioner, a tandem differential mobility analyzer (TDMA) and a scanning mobility particle sizing (SMPS) system. Results obtained from the observation of TDMA presented the deliquescence point of sodium chloride aerosol at 75% RH. In addition, the growth size of sodium chloride aerosol was observed to be 79.47 nm and the growth ratio was 77.94%, when the initial size of aerosol was 101.82 nm. Surfactants were internally mixed with sodium chloride at six different weight fractions, i.e. 2.5, 5, 10, 20, 40, and 60% by weight of surfactants in dry aerosol. Both surfactants apparently decreased the deliquescence point of sodium chloride, in which the lowest deliquescence point appeared at about 71% RH when the weight fraction of surfactants is 60% by weight of surfactants in dry aerosol. Moreover, the smallest size of sodium chloride aerosol with surfactants was 142.7 nm at 60% by weight of pyruvic acid in dry aerosol. Our results further demonstrate that the deliquescence point and size of sodium chloride aerosol with surfactants are related to the weight fraction of surfactants.

Aerosols↗
PubMed1995

Characterization of a mutation that abolishes quinone reduction by electron transfer flavoprotein-ubiquinone oxidoreductase.

Two mutant alleles of the gene encoding electron transfer flavoprotein-ubiquinone oxidoreductase were identified and characterized in fibroblasts from a patient with glutaric acidemia type II. One of these alleles is a C-T transition in the donor site of an intron that causes skipping of a 222 bp exon. Included in the missing 74 amino acids is C561, which is predicted to be one of the four cysteine ligands of the 4Fe4S cluster. This mutant allele does not encode a stable ETF-QO in human fibroblasts but, when expressed in Saccharomyces cerevisiae, the mutant ETF-QO is relatively stable and properly targeted to and processed by mitochondria. The mutant protein lacks ubiquinone reductase activity, but does accept electrons from ETF in the catalyzed disproportionation of ETF semiquinone. These data suggest that in the normal protein the flavin center accepts electrons from ETF and that the 4Fe4S cluster reduces ubiquinone. Deleting the 74 amino acids also alters the association between the protein and membrane such that the mutant ETF-QO cannot be extracted from the membrane using the same conditions used for wild type ETF-QO. A site directed mutant that contains only the single amino acid substitution, C561A, exhibits the same catalytic behavior as the deletion mutant, supporting the hypothesis regarding the specific functions of the two redox centers. It is, however, solubilized by the same conditions as wild type ETF-QO.

Alleles↗
PubMed2002

DNA microarrays with PAMAM dendritic linker systems.

The DNA microarray-based analysis of single nucleotide polymorphisms (SNPs) is important for the correlation of genetic variations and individual phenotypes, and for locating disease-causing genes. To facilitate the development of surfaces suitable for immobilization of oligonucleotides, we report here a novel method for the surface immobilization of DNA using pre-fabricated polyamidoamine (PAMAM) starburst dendrimers as mediator moieties. Dendrimers containing 64 primary amino groups in their outer sphere are covalently attached to silylated glass supports and, subsequently, the dendritic macromolecules are modified with glutaric anhydride and activated with N-hydroxysuccinimide. As a result of the dendritic PAMAM linker system the surfaces reveal both a very high immobilization efficiency for amino-modified DNA-oligomers, and also a remarkable high stability during repeated regeneration and re-using cycles. The performance of dendrimer-based DNA microarrays in the discrimination of SNPs is demonstrated.

Anhydrides↗