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1.
Rabbit erythrocytes contain a soluble aspartyl β-carboxyl methyltransferase capable of specifically carboxyl methylating the β-carboxyl group of an internal aspartyl residue in the synthetic polypeptide eledoisin, a hypotensively active peptide from the cephalopodsEledone moschata andE. aldrovandi, and tetragastrin, the biologically active C-terminal tetrapeptide of human gastrin. However, the aspartyl residue in delta sleep-inducing peptide (DSIP) could not be carboxyl methylated, nor could glutamyl residues in any polypeptide tested. 相似文献
2.
Shoichiro Ozaki Etsuko Ebisui Kozo Hamada Jun-Ichi Goto Akinobu Z. Suzuki Akiko Terauchi Katsuhiko Mikoshiba 《Bioorganic & medicinal chemistry letters》2010,20(3):1141-1144
Aryl β-aminoethyl ketones were discovered as potent inhibitors of tissue transglutaminase. Heteroaryl-like thiophene groups and N-benzyl N-t-butyl aminoethyl group are critical to the strong inhibitory activity of aryl β-aminoethyl ketones. 相似文献
3.
Ozaki S Ebisui E Hamada K Suzuki AZ Terauchi A Mikoshiba K 《Bioorganic & medicinal chemistry letters》2011,21(1):377-379
Potent transglutaminase inhibitors were obtained from disulfide compounds, cystamine, dimethyl cystine, and dimethyl homocystine. The disulfide bond and thiophene ring play an important role in inhibitory activity of synthesized aryl β-amino ketones. 相似文献
4.
Dos Santos AL 《World journal of biological chemistry》2010,1(2):21-30
Cells of Candida albicans (C. albicans) can invade humans and may lead to mucosal and skin infections or to deep-seated mycoses of almost all inner organs, especially in immunocompromised patients. In this context, both the host immune status and the ability of C. albicans to modulate the expression of its virulence factors are relevant aspects that drive the candidal susceptibility or resistance; in this last case, culminating in the establishment of successful infection known as candidiasis. C. albicans possesses a potent armamentarium consisting of several virulence molecules that help the fungal cells to escape of the host immune responses. There is no doubt that the secretion of aspartyl-type proteases, designated as Saps, are one of the major virulence attributes produced by C. albicans cells, since these hydrolytic enzymes participate in a wide range of fungal physiological processes as well as in different facets of the fungal-host interactions. For these reasons, Saps clearly hold promise as new potential drug targets. Corroborating this hypothesis, the introduction of new anti-human immunodeficiency virus drugs of the aspartyl protease inhibitor-type (HIV PIs) have emerged as new agents for the inhibition of Saps. The introduction of HIV PIs has revolutionized the treatment of HIV disease, reducing opportunistic infections, especially candidiasis. The attenuation of candidal infections in HIV-infected individuals might not solely have resulted from improved immunological status, but also as a result of direct inhibition of C. albicans Saps. In this article, we review updates on the beneficial effects of HIV PIs against the human fungal pathogen C. albicans, focusing on the effects of these compounds on Sap activity, growth behavior, morphological architecture, cellular differentiation, fungal adhesion to animal cells and abiotic materials, modulation of virulence factors, experimental candidiasis infection, and their synergistic actions with classical antifungal agents. 相似文献
5.
《Mutation Research/Genetic Toxicology》1986,169(1-2):1-9
Mesityl oxide and isophorone, two β-methylated-α,β-unsaturated industrial solvent ketones, were found to be converted to mutagens by aqueous chlorination under conditions of pH and reactant concentration that may be relevant to waste water and drinking water chlorination. Chlorination of millimolar concentrations of isophorone generated mutagens at a pH as low as 8.5, while mutagens were formed from submillimolar concentrations of mesityl oxide at pH 8.5, or millimolar concentrations at pH 7.5. It is suggested that mutagen formation can occur via a haloform reaction at such low pH levels because of extended resonance stabilization of an intermediate carbanion. 相似文献
6.
Aspartyl β-semialdehyde dehydrogenase (ASADH) is an important enzyme, occupying the first branch position of the biosynthetic
pathway of the aspartate family of amino acids in bacteria, fungi and higher plants. It catalyses reversible dephosphorylation
of l-β-aspartyl phosphate (βAP) to l-aspartate-β-semialdehyde (ASA), a key intermediate in the biosynthesis of diaminopimelic acid (DAP)—an essential component
of cross linkages in bacterial cell walls. Since the aspartate pathway is unique to plants and bacteria, and ASADH is the
key enzyme in this pathway, it becomes an attractive target for antimicrobial agent development. Therefore, with the objective
of deducing comparative structural models, we have described a molecular model emphasizing the uniqueness of ASADH from Mycobacterium tuberculosis (H37Rv) that should generate insights into the structural distinctiveness of this protein as compared to structurally resolved
ASADH from other bacterial species. We find that mtASADH exhibits structural features common to bacterial ASADH, while other structural motifs are not present. Structural analysis
of various domains in mtASADH reveals structural conservation among all bacterial ASADH proteins. The results suggest that the probable mechanism
of action of the mtASADH enzyme might be same as that of other bacterial ASADH. Analysis of the structure of mtASADH will shed light on its mechanism of action and may help in designing suitable antagonists against this enzyme that could
control the growth of Mycobacterium tuberculosis.
Anupama Singh and Hemant R. Kushwaha contributed equally to this work. 相似文献
7.
Tomasz Janeczko Jadwiga Dmochowska-Gładysz Edyta Kostrzewa-Susłow 《World journal of microbiology & biotechnology》2010,26(11):2047-2051
Enantiospecific microbial reduction of bicyclic ketones was described. Racemic Wieland–Miescher (1) and Hajos–Parrish (2) ketones were used as substrates. In a 4-h biotransformation of Hajos–Parrish ketone (2) using the strain of Didymosphaeria igniaria an optically pure ketone (R)-2 was obtained, whereas the (S)-2 ketone underwent reduction to (4aS,5S)-4 alcohol with 100% of enantiomeric excess and with over 60% of diastereoisomeric excess. Jones oxidation of the alcohol obtained
in the biotransformation gave an optically pure ketone (S)-2. Enzymatic system of Coryneum betulinum reduced the (R)-2 ketone to (4aR,5S)-4 alcohol with a high enantiomerical purity in a 6-day reaction. Wieland-Miescher (1) ketone was transformed by these microorganisms in an analogous way, but the reaction times were longer. 相似文献
8.
Sadakane Y Fujii N Nakagomi K 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(29):3240-3246
The major soluble eye lens protein, αA-crystallin, has a very long half-life. Thus, many post-translational modifications, including stereoinversion, have been found in its constituent amino acids. We determine the rates of β-linkage isomerization, which is the main reaction through the formation of a succinimide intermediate, of specific Asp residues of recombinant human αA-crystallin protein by simple RP-HPLC method. Kinetic analyses of the β-linkage isomerization were performed on the three Asp residues of αA-crystallin, (58)Asp, (84)Asp, and (151)Asp, because the d/l ratios of both the (58)Asp and (151)Asp residues were higher than 1.0 in the αA-crystallin isolated from aged human eye lens. The β-linkage isomerizations of both the (58)Asp and (84)Asp residues were suppressed in the recombinant protein by approximately 0.4-0.5 times compared to those in the synthetic peptide below 50 °C, whereas the isomerization of the (151)Asp residue occurred at the same rate for the whole protein and synthetic fragmentary peptide. The suppression of (58)Asp isomerization in the recombinant protein relaxed to some extent when the αA-crystallin protein was incubated at a high temperature. The far-UV CD spectra showed that the secondary structure of the protein was partially disordered at temperatures greater than 60 °C in the recombinant αA-crystallin protein. These results suggest that the (58)Asp residue was restrained from forming the succinimide intermediate by the higher order structure of the αA-crystallin protein, and that the structural environment around the (151)Asp residue of the αA-crystallin was similar to that of the synthetic fragmentary peptide with respect to succinimide formation. The difference in the influence of the secondary structure of the αA-crystallin protein inverts the order of the succinimide formations of the (58)Asp and (151)Asp residues in the recombinant protein as compared with the order in the synthetic fragmentary peptides. 相似文献
9.
Kim MK Lee HS Kim S Cho SY Roth BL Chong Y Choo H 《Bioorganic & medicinal chemistry》2012,20(2):1139-1148
The well-known 5-HT(1A)/5-HT(7) selectivity issue was tackled by a new series of 4-aminoethylpiperazinyl aryl ketones (1a-1l) specifically designed to distinguish the two hydrophobic sites centered at the anchoring salt bridge. The 4-aminoethylpiperazinyl aryl ketones showed a wide spectrum of activity and selectivity for the 5-HT receptors depending on the type of the hydrophobic groups attached at the aryl piperazinyl ketone scaffold. Docking study of the most active compounds against 5-HT(7)R and 5-HT(1A)R revealed that both receptors have two hydrophobic pockets around the anchoring salt bridge. These two binding sites are perpendicular to each other in 5-HT(7)R but parallel in 5-HT(1A)R, and this observation is well matched with the previous report which claimed that 5-HT(7)R affinity arises from bent conformation of the bound ligand whereas an extended one is best suited for 5-HT(1A)R selectivity. Also, as these pockets have different size and shape, inhibitory activity as well as selectivity of the 4-aminoethylpiperazinyl aryl ketones against 5-HT(7)R and 5-HT(1A)R seemed to be determined by combination of two hydrophobic substituents attached at both ends of the title compounds. 相似文献
10.
Mori Y Aki K Kuge K Tajima S Yamanaka N Kaji Y Yamamoto N Nagai R Yoshii H Fujii N Watanabe M Kinouchi T Fujii N 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(29):3303-3309
UV-B irradiation is one of the risk factors in age-related diseases. We have reported that biologically uncommon D-β-Asp residues accumulate in proteins from sun-exposed elderly human skin. A previous study also reported that carboxymethyl lysine (CML; one of the advanced glycation end products (AGEs)) which is produced by the oxidation of glucose and peroxidation of lipid, also increases upon UV B irradiation. The formation of D-β-Asp and CML were reported as the alteration of proteins in UV B irradiated skin, independently. In this study, in order to clarify the relationship between the formation of D-β-Asp and CML, immunohistochemical analysis using anti-D-β-Asp containing peptide antibodies and anti-CML antibodies was performed in UV B irradiated mice. Immunohistochemical analyses clearly indicated that an anti-D-β-Asp containing peptide antibody and anti-CML antibody reacted at a common area in UV B irradiated skin. Western blot analyses of the proteins isolated from UV B irradiated skin demonstrated that proteins of 50-70 kDa were immunoreactive towards antibodies for both D-β-Asp containing peptide and CML. These proteins were identified by proteomic analysis as members of the keratin families including keratin-1, keratin-6B, keratin-10, and keratin-14. 相似文献
11.
12.
Singh KN Singh P Singh P Lal N Sharma SK 《Bioorganic & medicinal chemistry letters》2012,22(13):4225-4228
An efficient asymmetric Michael addition of cyclic ketones to β-nitrostyrenes using secondary diamine as an organocatalyst derived from l-proline and (R)-α-methylbenzyl amine has been described. This pyrrolidine based catalyst 1 was found to be very effective to synthesize various γ-nitrocarbonyl compounds in good yield (up to 81%) with excellent stereoselectivity (up to >99:1 dr and >99% ee). 相似文献
13.
《Journal of Molecular Catalysis .B, Enzymatic》1998,4(1-2):47-52
α,β-unsaturated aryl ketones, 1a–12, have been submitted to the action of the fungus Beauveria bassiana (ATCC 7159) in growing conditions. The saturation of the double bond strictly depends from the substituent α to the carbonyl group. The saturated ketone is then oxidised in a Baeyer-Villiger type reaction. This new oxidative capacity of the fungus has been studied and the adaptability of the micro organism towards structural modifications has been investigated. 相似文献
14.
During reactions of 23-oxosapogenins and the corresponding isomeric 22-oxo-23-spiroketals with MCPBA in the presence of BF3·Et2O, equilibration occurs between the ketones. The Baeyer-Villiger type oxidation is followed by fragmentation to the dinorcholanic lactones and 3-methylbutyrolactone. The mechanistic aspects of these reactions in the 25R and 25S series are discussed. 相似文献
15.
《Bioorganic & medicinal chemistry letters》2014,24(11):2517-2520
A benzoylthiourea–pyrrolidine catalyst was developed for the asymmetric Michael addition of ketones to chalcones. The corresponding products were obtained in high yields with high level of diastereoselectivities (up to 99:1 dr) and high level of enantioselectivities (up to 94% ee) under mild conditions. 相似文献
16.
Goretti M Ponzoni C Caselli E Marchegiani E Cramarossa MR Turchetti B Forti L Buzzini P 《Bioresource technology》2011,102(5):3993-3998
The bioreduction of α,β-unsaturated ketones (ketoisophorone, 2-methyl- and 3-methyl-cyclopentenone) and aldehydes [(S)-(−)-perillaldehyde and α-methyl-cinnamaldehyde] by 23 “non-conventional” yeasts (NCYs) belonging to 21 species of the genera Candida, Cryptococcus, Debaryomyces, Hanseniaspora, Kazachstania, Kluyveromyces, Lindnera, Nakaseomyces, Vanderwaltozyma, and Wickerhamomyces was reported. The results highlight the potential of NCYs as whole-cell biocatalysts for selective biotransformation of electron-poor alkenes. A few NCYs exhibited extremely high (>90%) or even total ketoisophorone and 2-methyl-cyclopentenone bioconversion yields via asymmetric reduction of the conjugated CC bond catalyzed by enoate reductases. Catalytic efficiency declined after switching from ketones to aldehydes. High chemoselectivity due to low competing carbonyl reductases was also sometimes observed. 相似文献
17.
Paula Rodríguez María Barton Virginia Aldabalde Silvia Onetto Paola Panizza Pilar Menndez David Gonzalez Sonia Rodríguez 《Journal of Molecular Catalysis .B, Enzymatic》2007,49(1-4):8-11
Four strains of endophytic microorganisms isolated from carrot root were able to carry out the reduction of the carbonyl group with diverse degree of enantio-, and diasteroselectivity. Furthermore, biotransformation in the presence of bacterial inhibitor affects the stereochemical outcome of the reaction, and the concomitant addition of a yeast inhibitor results in a large decrease in the conversion percentage. These results indicate that endophytic microorganisms might be involved in the enantioselective reduction of ketones and ketoesters with fresh carrot root pieces. 相似文献
18.
Sehl T Simon RC Hailes HC Ward JM Schell U Pohl M Rother D 《Journal of biotechnology》2012,159(3):188-194
A rapid TTC-based screening assay for ω-transaminases was developed to determine the conversion of substrates with a 2-hydroxy ketone motif. Oxidation of the compounds in the presence of 2,3,5-triphenyltetrazolium chloride (TTC) results in a reduction of the colourless TTC to a red-coloured 1,3,5-triphenylformazan. The enzymatic reductive amination of a wide range of various aliphatic, aliphatic-aromatic and aromatic-aromatic 2-hydroxy ketones can be determined by the decrease of the red colouration due to substrate consumption. The conversion can be quantified spectrophotometrically at 510 nm based on reactions, e.g. with crude cell extracts in 96-well plates. Since the assay is independent of the choice of diverse amine donors a panel of ω-transaminases was screened to detect conversion of 2-hydroxy ketones with three different amine donors: l-alanine, (S)-α-methylbenzylamine and benzylamine. The results could be validated using HPLC and GC analyses, showing a deviation of only 5-10%. Using this approach enzymes were identified demonstrating high conversions of acetoin and phenylacetylcarbinol to the corresponding amines. Among these enzymes three novel wild-type ω-transaminases have been identified. 相似文献
19.
Sang-Woo Han 《Bioscience, biotechnology, and biochemistry》2013,77(10):1788-1790
Removal of a side product to overcome unfavorable equilibrium is a prerequisite for the asymmetric amination of ketones using ω-transaminase (ω-TA). Alanine has been preferred as an amino donor because its deamination product (i.e. pyruvate) is easily removable by several enzymatic methods. Here, we demonstrated that the removal of pyruvate by an innate metabolic pathway could afford equilibrium shift of the ω-TA reactions. 相似文献
20.
《Process Biochemistry》2014,49(7):1107-1112
Aromatic β-amino ketones/alcohols such as adrenalone play an important role in some stereoselective synthesis of pharmaceuticals. Unfortunately, the transformation of aromatic β-amino ketones to their chiral alcohols has been carried out chemically as no corresponding biocatalyst has been available. Here, a novel carbonyl reductase responsible for the reduction of adrenalone to (R)-(−)-epinephrine was identified and characterized from Kocuria rhizophila. This enzyme was purified to homogeneity by ammonium sulfate precipitation followed by ion-exchange column chromatography, hydrophobic chromatography and gel chromatography. The purified enzyme yielded pure (R)-enantiomer product with high activity and utilized NADH as the cofactor. The enzyme had special significance by showing selectivity for many aromatic β-amino ketones/alcohols such as 2-amino-acetophenone, 2-amino-4′-hydroxyacetophenone, isoproterenol and ephedrine. The maximum reaction rate (Vmax) and apparent Michaelis–Menten constant (Km) for adrenalone and NADH were 14.62 μmol/(min mg) protein and 0.189 mM, 11.66 μmol/(min mg) protein and 0.204 mM respectively. These properties ensure the enzyme a promising future for industrial application as a replacement of chemical synthesis of aromatic β-amino chiral alcohols. 相似文献