- In Situ Fluorogenic and Chromogenic Reactions for the Sensitive Dual-Readout Assay of Tyrosinase Activity
-
As a well-known copper-containing oxidase, tyrosinase has been anticipated to serve as the biomarker of skin diseases. We describe here an exquisite label-free fluorescent and colorimetric dual-readout assay of its activity, inspired by the specific oxidation ability of monophenolamine substrates to catecholamines and a unique fluorogenic reaction between resorcinol and catecholamines. By employing commercially available tyramine as the model substrate (dopamine as the product), it is found that the tyrosinase-incubated tyramine solution exhibits obvious pale yellow with intense blue fluorescence in the presence of resorcinol and O2, where the absorbance and fluorescence intensity are directly related to the concentration of added tyrosinase (i.e., the amount of conversion of tyramine to dopamine). The overall process of sensing tyrosinase activity takes less than 100 min at ambient temperature and pressure conditions with exceedingly simple operation procedure, explicit response mechanism, and formation of fluorophore with high quantum yield from scratch. Furthermore, such a convenient, rapid, cost-effective, and highly sensitive dual-readout assay exhibits promising prospect for the tyrosinase activity in extensive bioassays and clinic research as well as in screening potential tyrosinase inhibitors.
- Zhao, Jiahui,Bao, Xingfu,Wang, Shuang,Lu, Shasha,Sun, Jian,Yang, Xiurong
-
-
Read Online
- Optimisation of nutritional requirements for dopamine synthesis by calcium alginate-entrapped mutant strain of Aspergillus oryzae EMS-6
-
The optimisation of nutritional requirements for dopamine (DA) synthesis by calcium alginate-entrapped mutant variant of Aspergillus oryzae EMS-6 using submerged fermentation technique was investigated. A total of 13 strains were isolated from soil. Isolate I-2 was selected as a better producer of DA and improved by exposing with ethyl methylsulphonate (EMS). EMS-6 was selected as it exhibited 43?μg/mL DA activity. The mutant variable was further treated with low levels of l-cysteine HCl to make it resistant against diversion and environmental stress. The conidiospores of mutant variant were entrapped in calcium alginate beads for stable product formation. EMS-6 gave maximum DA activity (124?μg/mL) when supplemented with 0.1% peptone and 0.2% sucrose, under optimised parameters viz. pH 3, temperature of 55?°C and incubation time of 70?min. The study involves the high profile of DA activity and is needed, as DA is capable to control numerous neurogenic disorders.
- Ali, Sikander,Nawaz, Wajeeha
-
-
Read Online
- Revisiting Boronate/Diol Complexation as a Double Stimulus-Responsive Bioconjugation
-
This study presents a quantitative assessment of the complexation between boronic acids and diols as a reversible and double-stimulus (oxidation and acidification)-responsive bioconjugation reaction. First, by using a competition assay, we have evaluated the equilibrium constants (water, pH 7.4) of 34 boronate/diol pairs, using diols of both aliphatic and aromatic (catechols) nature; in general, catechols were characterized by constants 3 orders of magnitude higher than those of aliphatic diols. Second, we have demonstrated that successful complexation with diols generated in situ via enzymatic reactions, and the boronate complexation was also employed to calculate the Michaelis-Menten parameters for two catechol-producing reactions: the demethylation of 3-methoxytyramine and the 2-hydroxylation of estradiol, respectively, mediated by P4502D6 and P4501A2. Third, we have prepared phenylboronic acid-functionalized hyaluronic acid (HA) and demonstrated the pH and H2O2-responsive character of the adducts that it formed with Alizarin Red S (ARS) used as a model catechol. The versatility and selectivity of the complexation and the mild character of the chemical species involved therefore make the boronate/catechol reaction an interesting candidate for bioconjugation purposes.
- Gennari, Arianna,Gujral, Chirag,Hohn, Erwin,Lallana, Enrique,Cellesi, Francesco,Tirelli, Nicola
-
-
Read Online
- Photoactivatable Dopamine and Sulpiride to Explore the Function of Dopaminergic Neurons and Circuits
-
Kinetic analysis of dopamine receptor activation and inactivation and the study of dopamine-dependent signaling requires precise simulation of the presynaptic release of the neurotransmitter dopamine and tight temporal control over the release of dopamine receptor antagonists. The 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group was conjugated to dopamine and the dopamine receptor antagonist sulpiride to generate "caged" versions of these neuromodulators (CyHQ-O-DA and CyHQ-sulpiride, respectively) that could release their payloads with 365 or 405 nm light or through 2-photon excitation (2PE) at 740 nm. These compounds are stable under physiological conditions in the dark, yet photolyze rapidly and cleanly to yield dopamine or sulpiride and the caging remnant CyHQ-OH. CyHQ-O-DA mediated the light activation of dopamine-1 (D1) receptors on the breast cancer cell line MDA-MB-231 in culture. In mouse brain slice from the substantia nigra pars compacta, localized flash photolysis of CyHQ-O-DA accurately mimicked the natural presynaptic release of dopamine and activation of dopamine-2 (D2) receptors, causing a robust, concentration-dependent, and repeatable G protein-coupled inwardly rectifying potassium channel-mediated outward current in whole-cell voltage clamp recordings that was amplified by cocaine and blocked by sulpiride. Photolysis of CyHQ-sulpiride rapidly blocked synaptic activity, enabling measurement of the unbinding rates of dopamine and quinpirole, a D2 receptor agonist. These tools will enable more detailed study of dopamine receptors, their interactions with other GPCRs, and the physiology of dopamine signaling in the brain.
- Asad, Naeem,Condon, Alec F.,Dore, Timothy M.,Gore, Sangram,Hampton, Shahienaz E.,Mclain, Duncan E.,Vijay, Sauparnika,Williams, John T.
-
p. 939 - 951
(2020/04/09)
-
- Oxidase-like MOF-818 Nanozyme with High Specificity for Catalysis of Catechol Oxidation
-
Despite the extensive studies of the nanozymes showing their superior properties compared to natural enzymes and traditional artificial enzymes, the development of highly specific nanozymes is still a challenge. The catechol oxidase specifically catalyzing the oxidations of o-diphenol to the corresponding o-quinone is important to the biosynthesis of melanin and other polyphenolic natural products. In this study, we first propose that MOF-818, containing trinuclear copper centers mimicking the active sites of natural catechol oxidase, shows efficient catechol oxidase activity with good specificity and no peroxidase-like characteristics. MOF-818 has good specificity and high catalytic activity as a novel catechol oxidase nanozyme.
- Chen, Jinxing,Dong, Shaojun,Fang, Youxing,Li, Minghua,Wu, Weiwei
-
supporting information
p. 15569 - 15574
(2020/10/18)
-
- The Study of Stability of Proline-Containing Derivatives of Dopamine and Serotonin in the Biological Media in Vitro Experiments
-
Abstract—: The peptides Boc-Gly-Pro-DP, Z-Gly-Pro-DP, LA-Gly-Pro-DP, Boc-Gly-Pro-Srt, Z-Gly-Pro-Srt have been synthesized for the first time. The study of their stability in the presence of leucine aminopeptidase, carboxypeptidase Y, carboxypeptidase B, and proline endopeptidase (PEP) has shown that the synthesized peptides are stable in the presence of aminopeptidases and carboxypeptidases. In the presence of PEP, dopamine (DP) and serotonin (Srt) have been cleaved from these substances. Thus, the originally synthesized proline derivatives of Srt and DP may be considered as the resources, from which Srt and DP can be gradually released. This creates the possibility of a prolonged action of these biologically active compounds on cells and, consequently, on the whole body.
- Andreeva, L. A.,Myasoedov, N. F.,Nagaev, I. Yu.,Shevchenko, K. V.,Shevchenko, V. P.
-
p. 150 - 158
(2020/05/28)
-
- Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids
-
The benzylisoquinoline alkaloids (BIAs) are an important group of secondary metabolites from higher plants and have been reported to show significant biological activities. The production of BIAs through synthetic biology approaches provides a higher-yielding strategy than traditional synthetic methods or isolation from plant material. However, the reconstruction of BIA pathways in microorganisms by combining heterologous enzymes can also give access to BIAs through cascade reactions. Most importantly, non-natural BIAs can be generated through such artificial pathways. In the current study, we describe the use of tyrosinases and decarboxylases and combine these with a transaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs, including six non-natural alkaloids, in cascades from l-tyrosine and analogues.
- Wang, Yu,Tappertzhofen, Nadine,Méndez-Sánchez, Daniel,Bawn, Maria,Lyu, Boyu,Ward, John M.,Hailes, Helen C.
-
supporting information
p. 10120 - 10125
(2019/06/27)
-
- Compositions and methods for producing benzylisoquinoline alkaloids
-
The present invention relates to host cells that produce compounds that are characterized as benzylisoquinolines, as well as select precursors and intermediates thereof. The host cells comprise one, two or more heterologous coding sequences wherein each of the heterologous coding sequences encodes an enzyme involved in the metabolic pathway of a benzylisoquinoline, or its precursors or intermediates from a starting compound. The invention also relates to methods of producing the benzylisoquinoline, as well as select precursors and intermediates thereof by culturing the host cells under culture conditions that promote expression of the enzymes that produce the benzylisoquinoline or precursors or intermediates thereof.
- -
-
Page/Page column 4
(2016/05/19)
-
- Kinetic and solvent isotope effects on biotransformation of aromatic amino acids and their derivatives
-
Aromatic amino acids such as l-phenylalanine, l-tryptophan, 3′,4′-dihydroxy-l-phenylalanine (l-DOPA), and their derivatives 3′,4′-dihydroxyphenylacelaldehyde (DOPAL) and 3′,4′-dihydroxyphenylethanol (DOPET), play an essential role in human metabolic processes. Incorrect or slow biotransformation of these compounds leads to some metabolic dysfunctions and in some cases to some neurodegenerative diseases. Therefore, studies of the biotransformation mechanisms of these metabolites draw biochemists' and medical researchers' attention. This study investigates the mechanisms of biotransformation of the aforementioned compounds using kinetic (KIE) and solvent (SIE) isotope effect methods. The overview presents the results and the numerical values of KIE and SIE methods, obtained in the study of biotransformation of l-phenylalanine, 5′-chloro-l-tryptophan, and l-DOPA, catalyzed by the enzymes from the lyases group (phenylalanine ammonia lyase, tryptophan indole-lyase, and tyrosine decarboxylase). Deuterium KIE was also determined during the deamination of 2′-chloro-l-phenylalanine in the presence of the enzyme l-phenylalanine dehydrogenase, as well as in the conversion of DOPAL into DOPET catalyzed by the enzyme alcohol dehydrogenase. The values of KIE and SIE have been determined using a noncompetitive spectrophotometric and a competitive (combined with internal radioactivity standard) radiometric methods.
- Kańska, Marianna,Jemielity, Jacek,Paj?k, Ma?gorzata,Pa?ka, Katarzyna,Podsadni, Katarzyna,Winnicka, El?bieta
-
p. 627 - 634
(2016/12/26)
-
- Tyrosol and hydroxytyrosol derivatives as antitrypanosomal and antileishmanial agents
-
Trypanosomiasis and leishmaniasis keep being a real challenge for health and development of African countries. Existing treatments have considerable side effects and increase resistance of the parasites. We have measured antitrypanosomal and antileishmanial activity of natural phenols, tyrosol (TYR) and hydroxytyrosol (HT) and several of their esters and metabolites. We found significant IC50 values against Trypanosoma brucei for HT decanoate ester and HT dodecanoate ester (0.6 and 0.36 μM, respectively). This represents a large increase in activity with respect to HT (79 and 132 fold, respectively). Moreover, both compounds displayed a high selectivity index against MRC-5, a non-tumoral human cell line (118 and 106, respectively). Then, we synthesized a focused library of compounds to explore structure-activity. We found the ether and thiourea analogs of HT decanoate ester and HT dodecanoate ester also showed IC50 values against T. brucei in the low micromolar range. In conclusion, the di-ortho phenolic ring and medium size alkyl chain are essential for activity whereas the nature of the chemical bond among them seems less important.
- Belmonte-Reche, Efres,Martínez-García, Marta,Pe?alver, Pablo,Gómez-Pérez, Verónica,Lucas, Ricardo,Gamarro, Francisco,Pérez-Victoria, José María,Morales, Juan Carlos
-
p. 132 - 140
(2016/05/24)
-
- A Method for Synthesizing a Catecholamine Using Plasma Polymerization
-
The present invention relates to a method for manufacturing a catecholamine-based compound using a plasma polymerization method and, more specifically, to a method for artificially synthesizing a unimolecular compound capable of having various catecholamines, i.e. a hydroxyl group (-OH) as a ortho-group of a benzene ring and various alkylamines as a para-group, from a catecholamine precursor material such as phenol, aniline, etc, using a dry plasma polymerization method.COPYRIGHT KIPO 2015
- -
-
Page/Page column 19
(2017/01/02)
-
- Investigation of a substrate-specifying residue within Papaver somniferum and Catharanthus roseus aromatic amino acid decarboxylases
-
Plant aromatic amino acid decarboxylases (AAADs) catalyze the decarboxylation of aromatic amino acids with either benzene or indole rings. Because the substrate selectivity of AAADs is intimately related to their physiological functions, primary sequence data and their differentiation could provide significant physiological insights. However, due to general high sequence identity, plant AAAD substrate specificities have been difficult to identify through primary sequence comparison. In this study, bioinformatic approaches were utilized to identify several active site residues within plant AAAD enzymes that may impact substrate specificity. Next a Papaver somniferum tyrosine decarboxylase (TyDC) was selected as a model to verify our putative substrate-dictating residues through mutation. Results indicated that mutagenesis of serine 372 to glycine enables the P. somniferum TyDC to use 5-hydroxytryptophan as a substrate, and reduces the enzyme activity toward 3,4-dihydroxy-L-phenylalanine (dopa). Additionally, the reverse mutation in a Catharanthus roseus tryptophan decarboxylase (TDC) enables the mutant enzyme to utilize tyrosine and dopa as substrates with a reduced affinity toward tryptophan. Molecular modeling and molecular docking of the P. somniferum TyDC and the C. roseus TDC enzymes provided a structural basis to explain alterations in substrate specificity. Identification of an active site residue that impacts substrate selectivity produces a primary sequence identifier that may help differentiate the indolic and phenolic substrate specificities of individual plant AAADs.
- Torrens-Spence, Michael P.,Lazear, Michael,Von Guggenberg, Renee,Ding, Haizhen,Li, Jianyong
-
-
- Brain-specific delivery of dopamine mediated by N, N-dimethyl amino group for the treatment of Parkinson's disease
-
Parkinson's disease (PD) has become one of the most deadly diseases due to a lack of effective treatment. Herein, N-3,4-bis(pivaloyloxy)dopamine-3- (dimethylamino)propanamide (PDDP), a brain-specific derivative of dopamine, was designed and synthesized, which consists of a brain targeted ligand, N,N-dimethyl amino group, and two dipivaloyloxy groups for lipophilic modification. PDDP was investigated both in vitro and in vivo by comparing with L-DOPA and another derivative (BPD) without N,N-dimethyl amino group. PDDP showed a more pronounced accumulation in mouse brain microvascular endothelial cells (bEnd.3) than BPD via an active transport process. The increased cellular uptake of PDDP was proven to be mediated by putative pyrilamine cationic transporters. Following intravenous administration, the concentration of PDDP in the brain was 269.28-fold and 6.41-fold higher than that of L-DOPA and BPD at 5 min, respectively. Additionally, PDDP effectively attenuated the striatum lesion caused by 6-hydroxydopamine (6-OHDA) in rats. More importantly, PDDP presented antioxidant and antiapoptotic effects on 6-OHDA-induced toxicity in human neuroblastoma cells (SH-SY5Y). Thus, N,N-dimethyl amino group-based PDDP represents an effective and safe treatment for PD.
- Li, Yanping,Zhou, Yangyang,Qi, Bowen,Gong, Tao,Sun, Xun,Fu, Yao,Zhang, Zhirong
-
p. 3174 - 3185
(2014/11/07)
-
- Biochemical evaluation of a parsley tyrosine decarboxylase results in a novel 4-hydroxyphenylacetaldehyde synthase enzyme
-
Plant aromatic amino acid decarboxylases (AAADs) are effectively indistinguishable from plant aromatic acetaldehyde syntheses (AASs) through primary sequence comparison. Spectroscopic analyses of several characterized AASs and AAADs were performed to look for absorbance spectral identifiers. Although this limited survey proved inconclusive, the resulting work enabled the reevaluation of several characterized plant AAS and AAAD enzymes. Upon completion, a previously reported parsley AAAD protein was demonstrated to have AAS activity. Substrate specificity tests demonstrate that this novel AAS enzyme has a unique substrate specificity towards tyrosine (km 0.46. mM) and dopa (km 1.40. mM). Metabolite analysis established the abundance of tyrosine and absence of dopa in parsley extracts. Such analysis indicates that tyrosine is likely to be the sole physiological substrate. The resulting information suggests that this gene is responsible for the in vivo production of 4-hydroxyphenylacetaldehyde (4-HPAA). This is the first reported case of an AAS enzyme utilizing tyrosine as a primary substrate and the first report of a single enzyme capable of producing 4-HPAA from tyrosine.
- Torrens-Spence, Michael P.,Gillaspy, Glenda,Zhao, Bingyu,Harich, Kim,White, Robert H.,Li, Jianyong
-
experimental part
p. 211 - 216
(2012/07/14)
-
- Hydroxylation of p-substituted phenols by tyrosinase: Further insight into the mechanism of tyrosinase activity
-
A study of the monophenolase activity of tyrosinase by measuring the steady state rate with a group of p-substituted monophenols provides the following kinetic information: kcatm and the Michaelis constant, KMm. Analysis of these data taking into account chemical shifts of the carbon atom supporting the hydroxyl group (δ) and σp+, enables a mechanism to be proposed for the transformation of monophenols into o-diphenols, in which the first step is a nucleophilic attack on the copper atom on the form Eox (attack of the oxygen of the hydroxyl group of C-1 on the copper atom) followed by an electrophilic attack (attack of the hydroperoxide group on the ortho position with respect to the hydroxyl group of the benzene ring, electrophilic aromatic substitution with a reaction constant ρ of -1.75). These steps show the same dependency on the electronic effect of the substituent groups in C-4. Furthermore, a study of a solvent deuterium isotope effect on the oxidation of monophenols by tyrosinase points to an appreciable isotopic effect. In a proton inventory study with a series of p-substituted phenols, the representation of kcatfn/kcatf0 against n (atom fractions of deuterium), where kcatfn is the catalytic constant for a molar fraction of deuterium (n) and kcatf0 is the corresponding kinetic parameter in a water solution, was linear for all substrates. These results indicate that only one of the proton transfer processes from the hydroxyl groups involved the catalytic cycle is responsible for the isotope effects. We suggest that this step is the proton transfer from the hydroxyl group of C-1 to the peroxide of the oxytyrosinase form (Eox). After the nucleophilic attack, the incorporation of the oxygen in the benzene ring occurs by means of an electrophilic aromatic substitution mechanism in which there is no isotopic effect.
- Munoz-Munoz, Jose Luis,Berna, Jose,Garcia-Molina, Maria del Mar,Garcia-Molina, Francisco,Garcia-Ruiz, Pedro Antonio,Varon, Ramon,Rodriguez-Lopez, Jose N.,Garcia-Canovas, Francisco
-
scheme or table
p. 228 - 233
(2012/10/18)
-
- METHOD FOR MULTIPLE QUANTIFICATION OF AMINO GROUP-CONTAINING NON-PEPTIDIC COMPOUND WITH HIGH EFFICIENCY AND HIGH SENSITIVITY AND KIT THEREFOR
-
A method of quantifying a target non-peptidic compound having an amino group contained in one or more biological samples, which comprises a step of producing a difference in the mass of the target non-peptidic compound between samples, by using a combination of two or more kinds of stable isotopes of a compound represented by the formula (I): wherein R1, R2 and R3 are the same or different and each is hydrogen, halogen or alkyl, or a salt thereof, as a labeling compound; and a kit and the like usable for such method.
- -
-
-
- The effect of the buffering capacity of the supporting electrolyte on the electrochemical oxidation of dopamine and 4-methylcatechol in aqueous and nonaqueous solvents
-
Dopamine was electrochemically oxidized in aqueous solutions and in the organic solvents N,N-dimethyl-formamide and dimethylsulfoxide containing varying amounts of supporting electrolyte and water, to form dopamine ortho-quinone. It was found that the electrochemical oxidation mechanism in water and in organic solvents was strongly influenced by the buffering properties of the supporting electrolyte. In aqueous solutions close to pH 7, where buffers were not used, the protons released during the oxidation process were able to sufficiently change the localized pH at the electrode surface to reduce the deprotonation rate of dopamine ortho-quinone, thereby slowing the conversion into leucoaminochrome. In N,N-dimethylformamide and dimethylsulfoxide solutions, in the absence of buffers, dopamine was oxidized to dopamine ortho-quinone that survived without further reaction for several minutes at 25 °C. The voltammetric data obtained in the organic solvents were made more complicated by the presence of HCl in commercial sources of dopamine, which also underwent an oxidation process. Copyright
- Chen, Shanshan,Tai, Kah Yieng,Webster, Richard D.
-
experimental part
p. 1492 - 1499
(2012/07/03)
-
- Facile surface immobilization of cell adhesive peptide onto TiO2 substrate via tyrosinase-catalyzed oxidative reaction
-
A facile method to immobilize bioactive molecules including phenol molecules onto TiO2 surfaces via tyrosinase-catalyzed oxidative reaction was developed for surface bio-functionalization of biomaterials.
- Park, Kyung Min,Park, Ki Dong
-
supporting information; experimental part
p. 15906 - 15908
(2012/07/28)
-
- Polymers with structure-defined functions
-
An alternating copolymer comprising a backbone of residues of a maleic anhydride derivative and those of a compound containing vinylic unsaturation, which also comprises residues of an active compound containing a nucleophilic group, bound to the backbone by a residue of the nucleophilic group, including such copolymer comprising residues of an active compound containing alcohol, thiol or amine group. The chemical and biological propertieis of actives, such as protease inhibitors, neurotransmitter drugs, and other small molecule active drugs, are enhanced, and new applications enabled. Also, artefacts, including a solid medical implant device, dressing or scaffold or a fluid adhesive or medicinal composition comprising such a polymer, and a method of use of such polymer, including a method for the treatment or prophylaxis of wounds
- -
-
-
- Does conjugation of antioxidants improve their antioxidative/anti- inflammatory potential?
-
A series of symmetric and asymmetric spermine (SPM) conjugates with all-trans-retinoic acid (ATRA), acitretin (ACI), (E)-3-(trioxsalen-4′-yl) acrylic acid (TRAA) and l-DOPA, amides of ACI, l-DOPA and TRAA with 1-aminobutane, benzylamine, dopamine and 1,12-diaminobutane as well as hybrid conjugates of O,O′-dimethylcaffeic acid (DMCA) with TRAA or N-fumaroyl-indole-3-carboxanilide (FICA) and 2-(2-aminoethoxy)ethanol were synthesized and their antioxidant properties were studied. The reducing activity (RA)% of the compounds were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay and found to be in the range 0-92(20 min)%/96(60 min)% at 100 μM, the most powerful being the conjugates l-DOPA-SPM-l-DOPA (8, RA = 89%/96%) and l-DOPA-dopamine (13, RA = 92%/92%). Conjugate DMCA-NH(CH2CH2O)2-FICA (14) was the most powerful LOX inhibitor with IC50 33.5 μM, followed by the conjugates ACI-NHCH2Ph (10, IC50 40.5 μM), ACI-SPM-TRAA (7, IC50 41.5 μM), DMCA-NH(CH2CH2O) 2-TRAA (15, IC50 65 μM), 13 (IC50 81.5 μM) and ACI-dopamine (11, IC50 87 μM). The most potent inhibitors of lipid peroxidation at 100 μM were the conjugates 15 (98%) and ACI-SPM-ACI (4, 97%) whereas all other compounds showed activities comparable or lower than trolox. The most interesting compounds, namely ATRA-SPM-ATRA (3), 4, 10, 11 and 15, as well as unconjugated compounds such as ATRA and dopamine, were studied for their anti-inflammatory activity in vivo on rat paw oedema induced by Carrageenan and found to exhibit, for doses of 0.01 mmol/mL of conjugates per Kg of rat body weight, weaker anti-inflammatory activities (3.6-40%) than indomethacin (47%) with conjugate 3 being the most potent (40%) in this series of compounds. The cytocompatibility of selected compounds was evaluated by the viability of RAMEC cells in the presence of different concentrations (0.5-50 μM) of the compounds. Conjugates 3 (IC50 2.6 μM) and 4 (IC50 4.7 μM) were more cytotoxic than the corresponding unconjugated retinoids ATRA (IC50 18.3 μM) and ACI (IC50 14.6 μM), whereas conjugate 15 (IC50 12.9 μM) was less cytotoxic than either DCSP (IC50 11.3 μM) or the tert-butyl ester of TRAA (IC50 2.9 μM).
- Hadjipavlou-Litina, Dimitra,Magoulas, George E.,Bariamis, Stavros E.,Drainas, Denis,Avgoustakis, Konstantinos,Papaioannou, Dionissios
-
experimental part
p. 8204 - 8217
(2011/02/25)
-
- [8-[Bis(carboxymethyl)aminomethyl]-6-bromo-7-hydroxycoumarin-4-yl]methyl Moieties as photoremovable protecting groups for compounds with COOH, NH 2, OH, and C-O functions
-
We introduce a variant of coumarin-based photoactivatable protecting groups and use it exemplarily for caging of a carboxylic acid, an amine, a phenol, and a carbonyl compound. The caged compounds are efficiently photolyzed at long-wavelength UV/vis irradiation. Compared to the corresponding (6-bromo-7-hydroxycoumarin-4-yl)methyl (Bhc) derivatives, the novel coumarin-type caged compounds are distinguished by (i) dramatically increased solubilities in aqueous buffers, (ii) lower pKa values of the C7 hydroxyl of the coumarin chromophore, thus permitting efficient photorelease at lower pH, and (iii) higher photolysis quantum yields in the case of photoprotected carbonyl compounds. The primary step of the photocleavages occurs with rate constants of about 109 s-1.
- Hagen, Volker,Kilic, Funda,Schaal, Janina,Dekowski, Brigitte,Schmidt, Reinhard,Kotzur, Nico
-
scheme or table
p. 2790 - 2797
(2010/08/03)
-
- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
-
The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
- -
-
-
- Analysis of dopamine and tyrosinase activity on Ion-Sensitive Field-Effect Transistor (ISFET) devices
-
Dopamine (1) and tyrosinase (TR) activities were analyzed by using chemically modified ion-sensitive fieldeffect transistor (ISFET) devices. In one configuration, a phenylboronic acid functionalized ISFET was used to analyze 1 or TR. The formation of the boronate-1 complex on the surface of the gate altered the electrical potential associated with the gate, and thus enabled 1 to be analyzed with a detection limit of 7×10-5 M. Similarly, the TR-induced formation of 1, and its association with the boronic acid ligand allowed a quantitative assay of TR to be performed. In another configuration, the surface of the ISFET gate was modified with tyramine or 1 to form functional surfaces for analyzing TRactivities. The TR-induced oxidation of the tyramine- or 1-functionalized ISFETs resulted in the formation of the redox-active dopaquinone units. The control of the gate potential by the redox-active dopaquinone units allowed a quantitative assay of TR to be performed. The dopaquinone-functionalized ISFETs could be regenerated to give the 1-modified sensing devices by treatment with ascorbic acid.
- Freeman, Ronit,Elbaz, Johann,Gill, Ron,Zayats, Maya,Willner, Itamar
-
p. 7288 - 7293
(2008/03/13)
-
- Azabicyclic-phenyl-fused-heterocyclic compounds for treatment of disease
-
The invention provides compounds of Formula I: wherein Azabicyclo is any of: These compounds may be in the form of pharmaceutical salts or compositions, and racemic mixtures or pure enantiomers thereof. The compounds of Formula I are useful in pharmaceuticals in which α7 is known to be involved.
- -
-
-
- Quinuclidines-substituted-multi-cyclic-heteroaryls for the treatment of disease
-
The invention provides compounds of Formula I: 1where in W is 2These compounds may be in the form of pharmaceutical salts or compositions, racemic mixtures, or pure enantiomers thereof. The compounds of Formula I are useful to treat diseases or conditions in which α7 is known to be involved.
- -
-
-
- Quinuclidine-substituted hetero-bicyclic aromatic compounds for the treatment of disease
-
The invention provides compounds of Formula I: wherein W0 is a bicyclic moiety and is These compounds may be in the form of pharmaceutical salts or compositions, may be in pure enantiomeric form or racemic mixtures, and are useful to treat diseases or conditions in which α7 is known to be involved.
- -
-
-
- Therapeutic methods utilizing naturally derived bio-active complexes and delivery systems therefor
-
Methods are disclosed for correcting biological information transfer in a patient in need of such therapy which comprise administration to a patient of a composition comprising a therapeutically effective amount of a biocomplex comprising at least one bioactive agent from each of the three informational blocks of biological information transfer, each agent being present in an amount sufficient to correct the biological information transfer of the patient under treatment and resulting in the resumption of normal cell metabolism, said amount being less than the buffering amount of said agent; together with a carrier therefor.
- -
-
-
- Enzymatically amplified voltammetric sensor for microliter sample volumes of salicylate
-
A new voltammetric sensing strategy for salicylate employing two enzymes and applicable to microliter sample volumes is demonstrated. The method involves the use of the enzyme salicylate hydroxylase to convert salicylate to catechol, which is oxidized at a carbon electrode. The product of this oxidation reaction, o-quinone, is then reduced by a second enzyme, glucose oxidase, to regenerate catechol. Reoxidation of catechol results in a signal that is amplified due to repeated cycling of catechol molecules between the oxidized and reduced states. This chemistry is implemented in two configurations. (i) A paper disk into which both enzymes have been absorbed is mounted on a coplanar three-electrode assembly for aqueous experiments. Determination of salicylate in a nonprescription dermatological product is demonstrated. (ii) A small solution volume confined directly on the coplanar electrodes is used for determination of salicylate in whole blood. The advantages of the use of two enzymes and of monitoring steady-state catalytic currents are discussed.
- Moore, Thea J.,Joseph, Melissa J.,Allen, Barry W.,Coury Jr., Louis A.
-
p. 1896 - 1902
(2007/10/02)
-
- Process for the preparation of (8As,12AS,13AS)-decahydroisoquino ((2,1-G) (1,6)-naphthyridin-8-one derivatives
-
The invention provides a process for preparing single enantiomers of compounds represented by the formula: STR1 and chiral acid addition salts thereof; wherein: X and Y are independently hydrogen; lower alkyl; lower alkoxy; or halo; or X and Y taken together is methylenedioxy or ethylene-1,2-dioxy; which includes reduction of a compound represented by the formula: STR2 to give a mixture of stereoisomers represented by the formula: STR3 wherein each wavy line independently represents a bond in either the α or β position; followed by dissolving the mixture of stereoisomers and a chiral resolving acid in a suitable solvent and allowing the solution to crystallize, giving a salt of the desired enantiomer.
- -
-
-
- Process for the preparation of 4-O-phosphates of dopamine and dopamine derivatives
-
A process for the preparation of 4-O-phosphates of dopamine and dopamine derivatives by treatment of a mixture of both 3-O-phosphate and 4-O-phosphate isomers with a strong mineral acid and optional esterification of the so obtained phosphoric ester of dopamine or dopamine derivatives is described.
- -
-
-
- 3-methoxy-4-hydroxyphenylglycol fluorescence polarization immunoassay
-
The present invention is directed to a fluoroescence polarization immunoassay for determining the 3-methoxy-4-hydroxyphenylglycol content in body fluids, to the various components needed for preparing and carrying out such an assay, and to methods of making these components. Specifically, tracers, immunogens and antibodies are disclosed, as well as methods for preparing them. The assay is conducted by measuring the degree of polarization of plane polarized light that has been passed through a sample containing antiserum and tracer.
- -
-
-
- Increasing 5-lipoxygenase inhibitory activities by oxidative conversion of o-methoxyphenols to catechols using a Cu2+ - ascorbic acid - O2 system
-
Several complicated o-methoxyphenols were oxidized with high selectivity to catechols by a Cu2+ - ascorbic acid - O2 system. In this way, the RBL-1 5-lipoxygenase inhibitory activities of o-methoxyphenols were greatly increased. [6]-Norgingerol (4), a novel compound derived from [6]-gingerol (3), shows promise as a lead compound for new drugs because of its high inhibitory potency (IC50 = 5.0 x 10-8 M).
- Aihara,Higuchi,Hirobe
-
p. 842 - 844
(2007/10/02)
-
- Preparation of a Deuterated Analogue of Tetrahydropapaveroline Suitable for Use as an Internal Standard for G.C./M.S. Analysis of this Alkaloid: Retro Pictet-Spengler Condensation
-
Attempts to prepare deuterated analogues of salsolinol and tetrahydropapaveroline by exchange procedures in D2O have demonstrated that the Pictet-Spengler reaction is a reversible process.Tetrahydropapaveroline can be readily obtained from papaverine by reduction with Zn/HCl followed by demethylation in a process which can conveniently be adopted to produce a (2H3)analogue.
- Clezy, Peter S.,Duncan, Mark W.,Smythe, George A.
-
p. 483 - 491
(2007/10/02)
-
- O2-Cu2+-ASCORBIC ACID: A NOVEL OXIDATION SYSTEM FOR THE HIGHLY SELECTIVE O-DEALKYLATION OF 2-ALKOXYPHENOLS
-
The novel oxidation system "O2-Cu2+-ascorbic acid" is a selective reagent for the oxidative O-dealkylation of 2-alkoxyphenols and affords catechols in good yield.KEYWORDS - O-dealkylation; ascorbic acid; copper ion; oxidation; 2-alkoxyphenol; vanillin; dopamine; guaiacol; catechol
- Aihara, Kazuhiro,Higuchi, Tsunehiko,Hirobe, Masaaki
-
p. 837 - 840
(2007/10/02)
-
- Mechanism of the Oxidation of Dopamine by the Hydroxyl Radical in Aqueous Solution
-
The hydroxyl radical (HO*) reacts with dopamine (4-(2-aminoethyl)-1,2-benzenediol) via one-electron oxidation producing o-semiquinone and o-semiquinone anion radicals, k = 5.9 * 109 M-1 s-1.Reaction of OH* with protonated dopamine (H+QH2) proceeds via addition to the aromatic ring, while reaction with deprotonated dopamine (H+QH-) proceeds via direct, one-electron oxidation.The isomeric hydroxycyclohexadienyl radicals formed via addition of HO* to H+QH2 yield three kinetically distinguishable groups (1- and 2-, or 3- and 6-, or 4- and 5-hydroxycyclohexadienyl radicals) with regard to rates of water elimination to produce semiquinone radicals; dehydration is "very fast" (addition of OH* ipso to an OH group), "fast" or "slow".The fast and slow reactions are acid and base catalyzed, with minimum rates at pH 4-5.Acid catalysis appears to be specific, while base catalysis is general.Spectra were determined for the initial products of HO* reaction with H+QH2 at pH 3.1 and 4.7.Deprotonation of the HO* adducts is the rate-controlling step in the base-catalyzed water loss at pH 2-, HO-, and PO43- were 1.7 * 102, 6.5 * 108, 11, and 11 M-1 s-1, respectively; for the last reaction, rate constants for H2O and HPO42- were 1.1 * 103 and 2.2 * 108 M-1 s-1, respectively.
- Richter, Helen W.,Waddell, Walter H.
-
p. 5434 - 5440
(2007/10/02)
-
- One-Electron Redox Potentials of Phenols. Hydroxy- and Aminophenols and Related Compounds of Biological Interest
-
The rate constants for reversible electron transfer between a series of substituted phenolate ions and anilines and various substituted phenoxyl or anilino radicals in aqueous solution were measured by observing the formation or depletion of the radicals involved.Nonequilibrium concentrations of the radicals were produced in the presence of the corresponding phenols or anilines by using the pulse radiolysis technique.The relaxation of the system to equilibrium was monitored by optical detection methods.From the equilibrium constants for one-electron transfer, the one-electron redox potentials (E2) for 38 phenolic or anilino type compounds were determined, many of which are natural products.The redox potentials are strongly influenced by electron-donating or -withdrawing substituents at the aromatic system.
- Steenken, S.,Neta, P.
-
p. 3661 - 3667
(2007/10/02)
-
- Aromatic L-Amino Acid Decarboxylase from Micrococcus percitreus Purification, Crystallization and Properties
-
An aromatic L-amino acid decarboxylase was crystallized from the cell free extract of Micrococcus percitreus.The purification procedure included protamine sulfate treatment, ammonium sulfate fractionation, DEAE-Sephadex column chromatography and Sephadex G-200 filtration.Crystals were obtained from a solution of the purified enzyme by addition of ammonium sulfate.The crystalline enzyme preparation was homogeneous as judged by ultracentrifugation and SDS-polyacrylamide gel electrophoresis.The molecular weight was determined to be approximately 101,000.The enzyme was evidently composed of two identical subunits of a molecular weight of 48,000.The enzyme catalyzed the stoichiometric conversion of L-tryptophan to tryptamine and CO2 in the presence of pyridoxal phosphate.The optimum pH was 9.0 for the conversion.The Km value and the maximum velocity of L-tryptophan decarboxylation were 2.4E-3 M and 44 μmol/min/mg of protein, respectively.This enzyme also catalyzed decarboxylation of 5-hydroxy-L-tryptophan, L-phenylalanine, L-tyrosine, 3,4-dihydroxy-L-phenylalanine, L-kynurenine and thier α-methyl amino acid derivatives.
- Nakazawa, Hidetsugu,Kumagai, Hidehiko,Yamada, Hideaki
-
p. 2543 - 2552
(2007/10/02)
-
- 1,2,3,4-Tetrahydroisoquinolines and the preparation thereof
-
1,2,3,4-tetrahydroisoquinolines have the formula: STR1 wherein R1 and R2 are each hydrogen, lower alkyl, lower alkenyl, acyl, aryl or ar(lower)alkyl, in which aryl and the aryl moiety of the ar(lower)alkyl may contain at least one substituent selected from the group consisting of halogen, lower alkoxy, amino, nitro, hydroxy, acyloxy, ar(lower)alkoxy, lower alkylenedioxy, halo(lower)alkyl, acylamino, ar(lower)alkylamino and aryl, and pharmaceutically acceptable salts thereof.
- -
-
-
- Hair dyeing composition containing an aryldiamine and a substituted catechol
-
A composition for use in the dyeing of keratinous fibre such as hair includes an aqueous anaerobic solution of an aryldiamine and a substituted catechol. Optionally, an aromatic coupling agent can also be incorporated in the composition to modify the shade of color produced. Anaerobic storage conditions can, for example, be maintained by packing the composition in an aerosol container with a halocarbon propellant.
- -
-
-