18875-48-4Relevant academic research and scientific papers
Detection of Localized Hepatocellular Amino Acid Kinetics by using Mass Spectrometry Imaging of Stable Isotopes
Arts, Martijn,Soons, Zita,Ellis, Shane R.,Pierzchalski, Keely A.,Balluff, Benjamin,Eijkel, Gert B.,Dubois, Ludwig J.,Lieuwes, Natasja G.,Agten, Stijn M.,Hackeng, Tilman M.,van Loon, Luc J. C.,Heeren, Ron M. A.,Olde Damink, Steven W. M.
, p. 7146 - 7150 (2017)
Mass spectrometry imaging (MSI) simultaneously detects and identifies the spatial distribution of numerous molecules throughout tissues. Currently, MSI is limited to providing a static and ex vivo snapshot of highly dynamic systems in which molecules are constantly synthesized and consumed. Herein, we demonstrate an innovative MSI methodology to study dynamic molecular changes of amino acids within biological tissues by measuring the dilution and conversion of stable isotopes in a mouse model. We evaluate the method specifically on hepatocellular metabolism of the essential amino acid l-phenylalanine, associated with liver diseases. Crucially, the method reveals the localized dynamics of l-phenylalanine metabolism, including its in vivo hydroxylation to l-tyrosine and co-localization with other liver metabolites in a time course of samples from different animals. This method thus enables the dynamics of localized biochemical synthesis to be studied directly from biological tissues.
Transmucosal delivery of leucine enkephalin: Stabilization in rabbit enzyme extracts and enhancement of permeation through mucosae
Sayani,Chun,Chien
, p. 1179 - 1185 (1993)
Leucine enkephalin (Tyr-Gly-Gly-Phe-Leu; Leu-Enk) is a naturally occurring peptide that has been shown to have pain modulating properties. To evaluate the feasibility of using various absorptive mucosae as a route of systemic delivery, the stability of Leu-Enk and the effect of enzyme inhibitors (e.g., amastatin, EDTA, and thimerosal) on stabilization and permeation of Leu-Enk through rabbit mucosae in the presence of dihydrofusidates were investigated. Enzymes in the nasal, rectal, and vaginal mucosae were extracted and Leu-Enk (50 μg/mL) was added to each of the enzyme extracts and incubated to determine the kinetics and mechanism of degradation. The rate of degradation in the extracts in the absence of inhibitors followed the order: rectal > vaginal > nasal. Whereas EDTA had the best stabilizing effect on Leu-Enk, thimerosal was the best stabilizer for the degradation intermediates. A combination of amastatin (50 μM), EDTA (5 mM), and thimerosal (50 μM) had the greatest stabilizing effect on Leu-Enk and its degradation intermediates. For permeation studies, each mucosa was mounted onto a Valia-Chien permeation cell with Leu-Enk (200 μg/mL) in isotonic phosphate buffer (as donor solution). The enhancers used for the study were sodium tauro-dihydrofusidate (STDHF), sodium glycodihydrofusidate (SGDHF), and phosphato-dihydrofusidate (PHDHF). The greatest effect was achieved by PHDHF for all the mucosae. STDHF had a significant effect only on the rectal permeation, whereas SGDHF had significant effects on rectal and vaginal mucosae. Mechanisms by which the dihydrofusidates enhance permeation may involve micelle formation. Thus, the use of enzyme inhibitors and dihydrofusidates in combination has made transmucosal delivery of Leu-Enk a viable option.
Resolution of amino acids in a mixture of 2-methyl-2-propanol/water (19:1) catalyzed by alcalase via in situ racemization of one antipode mediated by pyridoxal 5-phosphate
Chen,Huang,Wang
, p. 7580 - 7581 (1994)
Procedures for the conversion of a racemic amino acid into the L-enantiomer by the alcalase catalyzed resolution of the amino acid ester in 2-methyl-2-propanol/water (19:1) simultaneously with the pyridoxal 5-phosphate-catalyzed racemization of the unhydrolyzed antipode have been developed.
Kinetic of adsorption and of photocatalytic degradation of phenylalanine effect of pH and light intensity
Elsellami,Vocanson,Dappozze,Puzenat,Pa?sse,Houas,Guillard
, p. 142 - 148 (2010)
Phenylalanine (Phe) was chosen to study the TiO2 photocatalytic degradation of amino acids, which are at the origin of the formation of odorous compounds after chlorination. The photocatalytic degradation has been investigated in aqueous solutions containing TiO2 suspensions as photocatalyst, in order to assess the influence of various parameters, such as adsorption, initial concentration, pH and radiant flux on the photocatalytic process. Results showed no correlation between dark adsorption and photocatalytic degradation. A multilayer kinetic was observed in the dark with a monolayer corresponding to less that 1% of OH covered, whereas Langmuir-Hinshelwood model seems to modelize the photocatalytic disappearance of Phe. However, even if the form of the curve is similar to L-H model, the degradation of phenylalanine is not a kinetic of L-H as we could plan it by considering the adsorption of the phenylalanine in the dark. The study of the mineralization of carbon and nitrogen showed that nitrogen atoms were predominantly photoconverted into NH4+ and a total mineralization of nitrogen and carbon seems occur. The identification of the by-products by LC-MS reveal mono- and di-hydroxylation and nitrogen-carbon (N-C) cleavage. The effect of pH showed an increase of adsorption under acid pH but a decrease of disappearance rate. The more efficient degradation was found at basic pH. The evolution of hydroxylated compounds of phenylalanine as a function of conversion revealed the presence of more hydroxylated compounds at natural pH and at basic pH compared to acid pH suggesting a modification of mechanism with solution pH. The effect of the radiant flux evaluated under different initial concentration of phenylalanine allowed us to determine that Κ increases by increasing the radiant flux, whereas Κ decreases or remains constant from about a value of 3.5 mW/cm2. The disappearance rate as a function of radiant flux has been showed to reach a maximal value corresponding to a maximal quantum yield of 1.6%.
A new tyrosine-specific chymotrypsin-like and angiotensin-degrading serine proteinase from Vipera lebetina snake venom
Siigur, Ene,T?nism?gi, Külli,Trummal, Katrin,Samel, Mari,Vija, Heiki,Aasp?llu, Anu,R?nnholm, Gunilla,Subbi, Juhan,Kalkkinen, Nisse,Siigur, Jüri
, p. 321 - 330 (2011)
Vipera lebetina venom contains different metallo- and serine proteinases that affect coagulation and fibrin(ogen)olysis. A novel serine proteinase from V. Lebetina venom having ChymoTrypsin Like Proteolytic activity (VLCTLP) was purified to homogeneity from the venom using Sephadex G-100sf, DEAE-cellulose, heparin-agarose and FPLC on Superdex 75 chromatographies. VLCTLP is a glycosylated serine proteinase with a molecular mass of 41926 Da. It reacts with N-acetyl-l-tyrosine ethyl ester (ATEE) but not with Suc-Ala-Ala-Pro-Phe-pNA or Suc-Ala-Ala-Pro-Leu-pNA. The complete amino acid sequence of the VLCTLP is deduced from the nucleotide sequence of the cDNA encoding this protein. The full-length cDNA sequence of the VLCTLP encodes open reading frame of 257 amino acid residues that includes a putative signal peptide of 18 amino acids, a proposed activation peptide of six amino acid residues and serine proteinase of 233 amino acid residues. VLCTLP belongs to the S1 (chymotrypsin) subfamily of proteases. The multiple alignment of its deduced amino acid sequence showed structural similarity with other serine proteases from snake venoms. The protease weakly hydrolyses azocasein, Aα-chain and more slowly Bβ-chain of fibrinogen. VLCTLP does not cleave fibrin and has no gelatinolytic activity. Specificity studies against peptide substrates (angiotensin I and II, oxidized insulin B-chain, glucagon, fibrinogen fragments etc.) showed that VLCTLP catalysed the cleavage of peptide bonds after tyrosine residues. VLCTLP is the only purified and characterized serine proteinase from snake venoms that catalyses ATEE hydrolysis. We detected ATEE-hydrolysing activities also in 9 different Viperidae and Crotalidae venoms.
Photolysis of phenylalanine in the presence of oxidized carbon nanotubes
Humeres, Eduardo,De Souza, Eduardo Pinheiro,Debacher, Nito Angelo,Moreira, Regina De F.P.M.,Lopes, Cristiane Nunes,Fernndez, Ma Isabel,Santaballa, J. Arturo,Canle, Moiss L.,Schreiner, Wido H.,Aliev, Abil E.
, p. 164 - 170 (2015)
Photolyses at 254 nm of phenylalanine (Phe) in aqueous solutions, were carried out in the presence of oxidized carbon nanotubes modified by the reaction with SO2 (mNTO). Kinetics of the photolyses were followed by UV spectrophotometry at 220 nm, and the products were characterized by HPLC, XPS, and 13C-SSNMR. The ratio of the initial rates of photolysis in the presence and absence of mNTO, k/ko, showed a systematic decrease. The photolytic decay of Phe occurs with minor formation of tyrosine. The mass of nanotubes produced an exponential attenuation of the photolytic decomposition of Phe. Total carbon analyses (TCA) showed no inorganic carbon formation after the photolyses. The first-order rate constant of photofunctionalization of mNTO by the insertion of phenylalanine onto the nanotube matrix was calculated from TCA to be kin = 30.1 min-1. Comparison of the XPS spectra of the mNTO before and after the photolysis, using the atom inventory technique, suggests the insertion of Phe along with the extrusion of a sulfide radical anion (?S-) which undergo subsequent oxidation to SO42-. The obtained results show the effects of mNTO on the photolysis of Phe and provide a new method of photofunctionalization of carbon materials, modified by the intermediates of the reduction of SO2, with an organic moiety.
Optimisation of the retroracemisation procedure for α-amino acids using (S)-2-[(N-alkylprolyl)amino]benzophenones, recyclable chiral axiliaries
De, Binod B.,Thomas, Neil R.
, p. 2687 - 2691 (1997)
The retroracemisation procedure developed by Belokon and coworkers has been re-examined using a variety of new (S)-2-[N-alkylprolyl)amino]benzophenone chiral auxiliaries. It has been found that (S)-2-[(N-benzylprolyl)amino] and (S)-2-[(N-1-(naphthalenyl-1-methyl)prolyl)amino] benzophenones ((S)-BPB and (S)-NPB) when used in conjunction with Ni(NO3)2·6H2O and a racemic α-amino acid preferentially form a single diastereoisomer in the presence of a mild base such as sodium methoxide. Decomposition of this complex under acidic conditions leads to the isolation of the (S)-amino acid in good yield, and in 55 to 99% e.e. The retroracemisation abilities of a polymer supported form of the (S)-BPB ligand have also been investigated and preliminary results for this are presented here.
Hydroxylation of Phenylalanine by Aqueous H2O2 in the Presence of an Artificial Water-soluble Iron Porphyrin Complex
Shimidzu, Takeo,Iyoda, Tomokazu,Kanda, Naoya
, p. 1206 - 1207 (1981)
Phenylalanine is hydroxylated by aqueous H2O2 in the presence of a catalytic amount of an artificial water-soluble iron porphyrin complex (1) to give monohydroxylated and dihydroxylated products, i.e., tyrosine and dihydroxyphenylalanine, which are obtained in good yields.
IMPROVED DEPROTECTION IN SOLID PHASE PEPTIDE SYNTHESIS: REMOVAL OF PROTECTING GROUPS FROM SYNTHETIC PEPTIDES BY AN SN2 MECHANISM WITH LOW CONCENTRATIONS OF HF IN DIMETHYLSULFIDE
Tam, James P.,Heath, William F.,Merrifield, R. B.
, p. 4435 - 4438 (1982)
The use of a low-concentration HF in dimethylsulfide (1:3, v/v) for the removal of protecting groups from synthetic peptides has been found to be efficient and to eliminate several side reactions associated with the high-concentration HF in anisole (9:1, v/v) normally employed in peptide synthesis.The mechanism of the low-concentration HF cleavage is SN2, in contrast to the SN1 mechanism of the high-concentration HF cleavage, and consequently the reaction proceeds without generation of carbocation intermediates.
Enzymatic Reactions in Aqueous-Organic media. XVII. Optical Resolution of Amino Acid Esters by Enzymatic Hydrolysis in Organic Solvents
Tomiuchi, Yoshimasa,Ohshima, Kouji,Kise, Hideo
, p. 2599 - 2603 (1992)
Enantiospecific hydrolysis of DL-tyrosine ethyl ester was carried out using α-chymotrypsin (CT) as a catalyst in organic solvents, and L-tyrosine was obtained with high optical purity.Activity and enantiospecificity of CT were found to be greatly altered by water content in the reaction media, and generally high enantiospecificity was observed at low water contents.Many of natural and unnatural amino acid esters were resolved by hydrolysis in organic solvents using CT, subtilisin Carlsberg, or subtilisin BPN' as catalysts.
