Amino Group In Position Research Articles

Surface‐modified gold electrodes for electrocatalytic oxidation of NADH based on the immobilization of phenoxazine and phenothiazine derivatives on self‐assembled monolayers

AbstractSelf‐assembled monolayers of cystamine and cysteine chemisorbed on gold electrode surfaces have been used as a support for covalent immobilization of some phenoxazine and phenothiazine derivatives. The covalent attachment was achieved after previous functionalization of the free amino groups on the electrode surface with bifunctional reagents (terephthaloyl chloride and 1,6‐hexamethylene diisocyanate) able to react with the imino form of the amino group in position 3 of the phenoxazine and phenothiazine derivatives.In every case, a shift of the redox potentials between 130 and 180 mV towards more positive potentials, as well as an increase in the peak‐topeak separation between anodic and cathodic peaks was observed after covalent attachment. The surface coverages (10−11 < Γ < 10−10 mol/cm2) obtained from the cyclic voltammograms were those for a not densely packed monolayer and varied depending on the redox compound immobilized. The surface‐modified electrodes obtained were afterwards used for the electrocatalytic oxidation of NADH.UV‐vis spectroscopy was used to monitor the successive steps of surface modification using gold semitransparent electrodes. The total surface coverage of redox mediator on the electrode surface could also be calculated from the optical difference spectra between the oxidized and the reduced state obtained ‘in situ’ in a spectroelectrochemical cell.

低水分系食品のばい焼過程における加熱反応生成物に及ぼす種々のアミノ酸の影響について

Effect various amino acids on the formation of 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4 (H)-pyran-4-one (DDMP) and 5-hydroxymethylfurfural (HMF) have been investigated using a model system of cookie baking. A mixture of fructose and each amino acid was heated at 150°C for 10min in a test tube. Each reaction mixture was extracted with 1ml of water, and the extracts were analyzed by HPLC. DDMP was the major product in this reaction. The position of amino group affected on the formation of DDMP, and the amount of DDMP from fructose and β-amino acids was much more than that from fructose and other amino acids such as α- and γ-amino acids. The carbon chain length of α-amino acids also affected on the formation of DDMP, and DDMP was generated most remarkably in the reaction between fructose and α-alanine. When the carbon chain length was longer than that of α-alanine, DDMP formation decreased gradually. N-substituted arginine and lysine formed a large quantity of DDMP in the reaction with fructose than their N-unsubstituted amino acids. Basic amino acids reacted strongly and quickly with the sugar, and arginine also generated DDMP in the earlier stage of the reaction with fructose than β-alanine.

Toluidine blue covalently immobilized onto gold electrode surfaces: An electrocatalytic system for nadh oxidation

AbstractThe electrochemical behavior of toluidine blue in solution has been studied and found to be strongly dependent on the electrode surface nature. Monolayers of cystamine (C) or 3‐mercaptopropionic acid (MP) chemisorbed onto gold electrode surfaces have been used as support for covalent attachment of toluidine blue (TOB) through its aromatic amino group in position 3 and the amino or carboxylic groups covering the elearode surface. After covalent attachment of TOB onto an MP monolayer, three different species remained stably attached to the electrode surface. Physically adsorbed TOB, which showed the same midpoint potential as in the solubilized state, E1/2 = –245 mV (Ag/AgCl); covalently attached TOB, whose midpoint potential was shifted toward 120 mV more positive potentials; and an unknown species, probably physically adsorbed TOB dimers, with a midpoint potential, E1/2 = +135 mV (Ag/AgCl).Toluidine blue modified electrodes started to oxidize catalytically NADH at –100 mV with an amperometric response dependent on the concentration of the substrate. An electrode fouling process was observed after successive additions of NADH leading to the loss of catalytic activity.

Reactivity of the amino groups in 3,3?-diamino-4,4?-di(p-aminophenoxy)diphenylsuIfone

Reactivities of the amino groups in 3,3′-diamino-4,4′-di(p-aminophenoxy)diphenylsulfone were estimated by MO calculations using the Paryzer-Parr-Pople method, by potentiometric measurement of their pKa values, and by the13C NMR spectroscopic study of the products obtained on reaction of the tetramine with two moles of 1,8-naphthalic anhydride. The results of these studies prove unambiguously the higher reactivity of the amino groups in positions 4 and 4′ of the phenoxide moieties.

Ring‐cleavage of isoxazoles with heterocyclic amines. Synthesis of fused pyrimidines

AbstractThe reaction between 2‐substituted ethyl 2,5‐dihydro‐5‐oxoisoxazole‐4‐carboxylates (2a,b) and heterocyclic amines 1, 4, and 6, having the amino group in position 2 with respect to the nuclear nitrogen afforded fused pyrimidines 3, 5, and 7.

Effect of some new cAMP analogs on cAMP-dependent protein kinase isoenzymes

1. 1. Ten new cAMP analogs were synthesized by replacing the purine ring with indazole, benzimidazole or benztriazole and/or their nitro and araino derivatives. 2. 2. Each analog proved effective in activating cAMP-dependent protein kinase I (PK-I) purified from rabbit skeletal muscle and cAMP-dependent protein kinase II (PK-II) from bovine heart and chasing 8-[ 3H]cAMP bound to regulatory subunits in the half-maximal effective concentrations of 2 × 10 −8-8 × 10 −6 M. 3. 3. The N-1-β- d-ribofuranosyl-indazole -3′5′- cyclophosphate(I) proved a very poor chaser and activator of both isoenzymes, but when indazole was attached at its N-2 to ribose (IV) or when its H at C-4 (equivalent to the position of amino-group in adenine) was substituted by an amino-(III) or especially nitro-group (II) its efficiency was dramatically increased. 4. 4. Analogs containing benztriazole ring proved as powerful as cAMP irrespective of the presence of substituents (VII–X). 5. 5. Benzimidazole derivatives with amino-(VI) or nitro-group (V) activated PK-II 3 and 20 times better than PK-I. 6. 6. Attaching of ribose to N-2 of indazole or benztriazole increased the affinity to PK-II 10 and 4 times, respectively. 7. 7. Chasing efficiency of cAMP analogs at half-saturating [ 3H]cAMP tended to correlate with activating potency only for PK-I but at saturating [ 3H]cAMP concentration for both isoenzymes. 8. 8. On the basis ofsynergistic activation with 8-Br-cAMP a site 2-selective binding ofnitro-benzimidazole (V) and unsubstituted benztriazole (VII) derivatives to PK-II is suggested.

New indole and triazino[5,4-b]indol-4-one derivatives: synthesis and studies as inotropics and inhibitors of blood platelet aggregation.

New triazino[5,4-b]indol-4-one derivatives carrying amino groups in position 3 were synthetized and tested as inotropic agents and inhibitors of platelet aggregation. 2h, 2p, 5p, and 6g are the most active as inotropic agents. Compounds were tested as inhibitors of platelet aggregation induced by adenosine 5'-diphosphate (ADP) and arachidonic acid (AA) (guinea pig whole blood). 2k, 2p, 5o, 6d, 6m, and 6o are the most active as inhibitors of the platelet aggregation induced by AA. 6d, 6h, and 6o are most active compounds also in the aggregation induced by ADP. Radioimmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on compounds 2b, 2d, 2f, 2g, 2h, 2i, 2k, 2m, 2o, 2p, 2r, 5i, 5j, 5k, 5r, and 5f, which inhibit platelet aggregation induced by AA. None of the compounds tested turned out to be selective inhibitors. Compounds 2h and 2p showed both inotropic and platelet aggregation inhibiting activity.

Structure-activity relationship of minoxidil analogs as inhibitors of lysyl hydroxylase in cultured fibroblasts

The structural features that confer upon minoxidil the ability to suppress lysyl hydroxylase activity in human skin fibroblasts were investigated. Substitution of the amino group in position 2 or 6 of the pyrimidine ring with a methyl group had no significant effect on the inhibitory activity of minoxidil, whereas substitution of both amino groups with methyl groups resulted in a complete loss of inhibitory activity. Together, these observations indicate that only one of the two amino groups ortho to the nitroxide oxygen is essential for the enzyme-suppressing effect of minoxidil. Derivatives of minoxidil formed by hydroxylation at position 3 or 4 of the piperidine ring were as active as the parent compound in suppressing lysyl hydroxylase activity. However, replacement of the piperidinyl group in position 4 of the pyrimidine ring with a pyrrolidinyl, morpholinyl, or N-methylpiperazinyl group resulted in loss of inhibitory activity, demonstrating that the piperidinyl group para to the nitroxide oxygen is essential for the enzyme-suppressing effect of minoxidil. Removing the nitroxide oxygen from position 1 of the pyrimidine ring resulted in a partial loss of the specificity of minoxidil for suppression of lysyl hydroxylase activity. The results indicate that distinct structural elements determine the enzyme-suppressing effect and the antihypertensive effect of minoxidil.

Synthesis and biological activities of neurokinin pseudopeptide analogues containing a reduced peptide bond

A series of pseudopeptides, analogues of neurokinin selective agonists, in which a peptide bond was replaced by a (CH 2NH) bond were synthesized. The biological activities of these compounds were determined on selective pharmacological preparations: the dog carotid artery for NK-1, the rabbit pulmonary artery devoid of endothelium for the NK-2 and the rat portal vein for the NK-3 receptors. The results reported in this study indicate that insertion of a pseudopeptide bond in various positions of these selective agonists resulted in a great decrease in potency compared to the parent compounds. Furthermore, the selectivity of agonists is maintained by the use of a methylene amino group in position 9–10 (Sar) for the NK-1 or in position 7–8 (MePhe) for the NK-3 selective compound. The selectivity is greatly diminished for the NK-2 analogues.

Preparation of pH sensors by covalent linkage of dye molecules to the surface of polystyrene optical fibers

AbstractFunctional Bromothymol Blue dyes containing amino groups in position 3 have been immobilized on the surface of chlorosulfonated polystyrene fibers and characterized by ESCA. Upon laser irradiation, a modified fiber has been used as an antenna fiber in a twisted pair of plastic optical fibers immersed in aqueous solutions having various pH. The light transmitted to the receiving fiber depends on pH values. This device can be used as a pH sensor.

Gentamycin resistance in Nicotiana conferred by AAC(3)-I, a narrow substrate specificity acetyltransferase.

Acetylation of the amino group in position 3 of the 2-desoxystreptamine moiety [AAC(3)] of gentamycin is a potent and wide-spread resistance mechanism in bacteria. Several marker genes coding for AAC(3) enzymes with varying substrate ranges or differing molecular properties have been identified. The enzymes AAC(3)-I and AAC(3)-II have a narrow substrate range and confer resistance to gentamycin and its close structural derivatives only, whereas genes encoding AAC(3)-III and AAC(3)-IV enzymes have a broad substrate range, modifying kanamycins, tobramycin, neomycin and paromomycin [1, 2]. Genes encoding AAC(3)-III and AAC(3)-IV enzymes were expressed in plants and shown to confer resistance to gentamicin, kanamycin (one of the genes), and possibly to other antibiotics [3]. Resistance to more than one antibiotic limits the use of the chimeric marker gene. We report that the narrow substrate range AAC(3)-I enzyme from the transposable element Tn21 [2] also provides a useful gentamycin resistance marker in plants. Materials and methods

Syntheses and in vitro evaluation of water-soluble "cationic metalloporphyrin-ellipticine" molecules having a high affinity for DNA

The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of linker (7-13 bonds), the chemical nature of the linking group (with a carboxamido or an ether function), the position of amino group between the two parts of hybrid molecules, the number of intercalator moieties (ellipticinium) covalently attached to the metalloporphyrin, and the nature of the central metal atom (Mn, Fe, Zn) on the biological activity of these hybrid molecules were studied. In addition, these molecules have a high affinity for double-stranded DNA (affinity constant of hybrid molecule 9Mn,Me = 2.3 x 10(9) M-1 for poly[d(A-T)] and 2.8 x 10(8) M-1 for poly[d(G-C)] and are cytotoxic against murine leukemia cells L1210 in vitro (IC50 of 9Mn,Me = 0.8 microM). Their cytotoxicities are dependent on the nature of central atom. Iron derivatives are less active than manganese analogues and the corresponding zinc derivatives are nearly inactive despite their same affinity for nucleic acids. These highly water-soluble hybrid molecules could be considered as efficient bleomycin models based on a cationic metalloporphyrin.

Possible control of transcript levels by chlorophyll precursors in Chlamydomonas.

Steady-state mRNA levels of the three nuclear genes cab1, rbcS1 and rbcS2 (coding for the light-harvesting chlorophyll-binding protein (LHCP) and the small subunit of ribulose 1,5-bisphosphate carboxylase, respectively) and of the two plastid-encoded genes rbcL and psaA2 (coding for the large subunit of the carboxylase and a member of the P700 chlorophyll a protein, respectively) have been investigated in synchronized Chlamydomonas cells in response to light and inhibitors interfering with chlorophyll synthesis. The accumulation of cab1, rbcS1 and psaA2 transcripts is light-dependent, whereas transcripts from rbcS2 and rbcL genes are present in high amounts in the light and in the dark. Dioxoheptanoic acid, an inhibitor blocking chlorophyll synthesis prior to porphyrin formation, does not affect the accumulation of all five mRNAs. However, inhibition of chlorophyll synthesis by incubating cells with dipyridyl, cycloheximide or nitrogen promotes the accumulation of porphyrin compounds, but specifically prevents the accumulation of light-dependent transcripts. Although functionally unrelated, these inhibitors are known to block an Fe-dependent oxygenase, which is involved in the formation of the isocyclic ring in the chlorophyll molecule. The data are explained as a control by chlorophyll precursors over the accumulation of light-dependent transcripts.

Pharmacological activities of two new histamine analogs.

The pharmacological properties of 2-aminohistamine and 2-amino-5-methylhistamine were studied and compared with those of histamine, 5-methylhistamine and dimaprit. The introduction of an amino group in position 2 of the histamine imidazole ring caused a reduction of histamine potency, mostly with respect to H1 receptors. Such disactivation was much more evident in its corresponding 5-methyl derivative. The pharmacological activity related to the chemical structure will be discussed in the paper.

Metabolic activation of polycyclic aromatic hydrocarbons by human colonic mucosa and Bacteroides fragilis

Abstract The Ames Salmonella mutagenicity assay has been used to assess the metabolic activation of the following polycyclic aromatic hydrocarbons by human colonic microsomes (S9) and a cell‐free extract of Bacteroides fragilis (Bf): 2‐aminoanthracene, 1‐naphthylamine, 2‐naphthylamine, 2‐aminofluorene, 2‐acetylaminofluorene, anthracene, benzo(a)pyrene, 3‐methylcholanthrene, 7, 12‐dimethylbenzanthracene, acridine, 9‐aminoacridine and 3‐methylindole.2‐Aminoanthracene and 2‐aminofluorene were the only compounds activated. In both cases, activation was dose‐dependent and 2‐aminofluorene exhibited synergistic activation by S9+Bf, as has previously been demonstrated with 2‐aminoanthracene.The organospecific aliphatic colonic carcinogen, 1, 2‐dimethylhydrazine was not activated in this system. Metabolic activation by S9+Bf is thus restricted to aromatic compounds with three rings and an amino group in position 2.These findings are consistent with enzymic substrate specificity, and are compatible with an enzymic basis for activation of polycyclic aromatic hydrocarbons by B. fragilis, present in large concentrations in the colonic lumen, and colonic microsomes.

Gonadotropin releasing hormone activation is mediated by dimerization of occupied receptors

A dinitrophenyl (DNP)-derivative of a gonadotropin releasing hormone (GnRH) antagonist was prepared by chemical modification of the epsilon amino group in position 6 of [D-pGlu 1,D-Phe 2,D-Trp 3,D-Lys 6]GnRH with 1-fluoro-2,4-dinitrobenzene. The DNP-antagonist D-pGlu-D-Phe-D-Trp-Ser-Tyr-D-Lys(N ε-DNP)-Leu-Arg-Pro-Gly-NH 2, retained high affinity binding to the GnRH receptor of pituitary membrane preparations and exhibited antagonistic activity when assayed in cultured pituitary cells. Both antibodies against DNP and their Fab fragments were able to bind the DNP-antagonist. However, only the addition of bivalent antibodies (and not the Fab fragments) converted the DNP-antagonist to an agonist. These results suggest that divalency is a critical factor in GnRH action.

Hypolipidemic Activity of 4-Pyrimidinecarboxylic Acids in CF1 Mice

A series of 4-pyrimidinecarboxylic acids were evaluated for hypolipidemic activity in mice at 20–30 mg/kg/d ip. A number of these derivatives were observed to be active at this dose. Substitution of the hydroxyl group in position 2 and 6 of the 4-pyrimidinecarboxylic acid with a sulfhydryl and an amino group, respectively, led to a compound which produced a >40% reduction of serum cholesterol and triglyceride levels in mice. Similarly, a compound which was substituted with an amino group in position 2 and an isobutyl group in position 5 led to equally potent activity as a hypolipidemic agent.

ADDITION OF ORGANOMETALLICS TO α,β-UNSATURATED THIOCARBONYL COMPOUNDS. III. MICHAEL ADDITION OF ACTIVE METHYLENE COMPOUNDS TO THIOAMIDE AND DITHIOCARBAMATE VINYLOGS

Abstract α,β-Unsaturated thiocarbonyl compounds substituted by a secondary amino group in position β, such as thioamide and dithiocarbamate vinylogs, react with sodium derivatives of active methylene compounds CH2XY to give 1,4-addition compounds. Methylation of the 1,4-adducts is followed by elimination of the amine and leads to conjugate thioethers and ketene dithioacetals with functional groups X and Y at the end of the chain. Cyclization and hydrolysis of the adduct afford 2H-thiopyran derivatives.

Synthesis and some pharmacological properties of oxytocin and vasopressin analogues with sarcosine or N-methyl-L-alanine in position 7.

Eight analogues of oxytocin and arginine-vasopressin were synthesized, in which the proline residue in position 7 was replaced by either sarcosine or N-methylalanine; some of the pharmacological properties of these analogues were evaluated. In peptides containing a beta-mercaptopropionic acid residue in position 1, the additivity of the effects of deletion of the amino group in position 1 and of the above-noted replacements in position 7 on biological properties of these analogues was ascertained. All of the analogues were found to be potent in either antidiuretic or uterine activity and also selective in action. From the point of view of pharmacological properties, substitution of sarcosine in position 7 of oxytocin gave analogues with higher oxytocic and milk-ejecting activities than did the substitution of N-methylalanine. The opposite structure-activity relationship was observed with arginine-vasopressin, where the N-methylalanine-containing analogues were more potent than the sarcosine-containing analogues with respect to pressor activity and also, if not deaminated, with respect to antidiuretic activity.

ADDITION OF ORGANOMETALLICS ON α,β-UNSATURATED THIOCARBONYL COMPOUNDS II. MICHAEL ADDITION OF LITHIUM ENOLATES ON THIOAMIDE AND DITHIOCARBAMATE VINYLOGS AND THIOAROYLFORMAMIDINE

Abstract α,β-Unsaturated thiocarbonyl compounds substituted by a secondary amino group in position β, such as thioamide vinylogs, dithiocarbamate vinylogs or thioaroylformamidines react with lithium enolates of esters, ketones or amides to give 1,4-addition compounds. In the presence of magnesium bromide 1,4-adducts undergo an intramolecular cyclization to give 2H-thiopyranones. Methylation of the 1,4-adducts is followed by a stereospecific elimination of the amine and leads to (1-Z)-1,3-dienic carbonyl compounds: with thioamide vinylogs, δ-methylthio-α,β,γ,δ-diethylenic ketones, esters and amides are obtained. Dithiocarbamate vinylogs give the α-ethylenic ketene dithioacetals, with a carbonyl function in δ-position. Substituted dihydrothiophenes and thiazolines are prepared by the reaction of ethyl α-chloro-α-lithiopropionate with aminopropenethione and thioaroylformamidine respectively.