Glycine-containing Dipeptides Research Articles

The glycine-containing dipeptide leucine-glycine raises accumbal dopamine levels in a subpopulation of rats presenting a lower endogenous dopamine tone

Interventions that elevate glycine levels and target the glycine receptor (GlyR) in the nucleus Accumbens (nAc) reduce ethanol intake in rats, supposedly by acting on the brain reward system via increased basal and attenuated ethanol-induced nAc dopamine release. Glycine transport across the blood brain barrier (BBB) appears inefficient, but glycine-containing dipeptides elevate whole brain tissue dopamine levels in mice. This study explores whether treatment with the glycine-containing dipeptides leucine-glycine (Leu-Gly) and glycine-leucine (Gly-Leu) by means of a hypothesized, facilitated BBB passage, alter nAc glycine and dopamine levels and locomotor activity in two rodent models. The acute effects of Leu-Gly and Gly-Leu (1–1000 mg/kg, i.p.) alone or Leu-Gly in combination with ethanol on locomotion in male NMRI mice were examined in locomotor activity boxes. Striatal and brainstem slices were obtained for ex vivo HPLC analyses of tissue levels of glycine and dopamine. Furthermore, the effects of Leu-Gly i.p. (1–1000 mg/kg) on glycine and dopamine output in the nAc were examined using in vivo microdialysis coupled to HPLC in freely moving male Wistar rats. Leu-Gly and Gly-Leu did not significantly alter locomotion, ethanol-induced hyperlocomotor activity or tissue levels of glycine or dopamine, apart from Gly-Leu 10 mg/kg that slightly raised nAc dopamine. Microdialysis revealed no significant alterations in nAc glycine or dopamine levels when regarding all rats as a homogenous group. In a subgroup of rats defined as dopamine responders, a significant elevation of nAc dopamine (20%) was seen following Leu-Gly 10–1000 mg/kg i.p, and this group of animals presented lower baseline dopamine levels compared to dopamine non-responders. To conclude, peripheral injection of glycine-containing dipeptides appears inefficient in elevating central glycine levels but raises accumbal dopamine levels in a subgroup of rats with a lower endogenous dopamine tone. The tentative relationship between dopamine baseline and ensuing response to glycinergic treatment and presumptive direct interactions between glycine-containing dipeptides and the GlyR bear insights for refinement of the glycinergic treatment concept for alcohol use disorder (AUD).

Synthesis and antimycobacterial activity of N-(2-aminopurin-6-yl) and N-(purin-6-yl) amino acids and dipeptides

Synthetic routes to novel N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates with amino acids and glycine-containing dipeptides were developed. In vitro testing of 42 new and known compounds made it possible to reveal a series of N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates exhibiting significant antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium, Mycobacterium terrae, and multidrug-resistant M. tuberculosis strain isolated from tuberculosis patients in the Ural region (Russia). N-(2-Aminopurin-6-yl)- and N-(purin-6-yl)-glycyl-(S)-glutamic acids were the most active compounds.

A plausible simultaneous synthesis of amino acids and simple peptides on the primordial Earth.

Following his seminal work in 1953, Stanley Miller conducted an experiment in 1958 to study the polymerization of amino acids under simulated early Earth conditions. In the experiment, Miller sparked a gas mixture of CH4, NH3, and H2O, while intermittently adding the plausible prebiotic condensing reagent cyanamide. For unknown reasons, an analysis of the samples was not reported. We analyzed the archived samples for amino acids, dipeptides, and diketopiperazines by liquid chromatography, ion mobility spectrometry, and mass spectrometry. A dozen amino acids, 10 glycine-containing dipeptides, and 3 glycine-containing diketopiperazines were detected. Miller's experiment was repeated and similar polymerization products were observed. Aqueous heating experiments indicate that Strecker synthesis intermediates play a key role in facilitating polymerization. These results highlight the potential importance of condensing reagents in generating diversity within the prebiotic chemical inventory.

Reactivity of hydroxopentaaquarhodium(III) ion towards glycine-containing dipeptides in aqueous medium

Reactivity of hydroxopentaaquarhodium(III) ion towards glycine-containing dipeptides in aqueous medium

Mechanistic aspects of ligand substitution on [(H 2 O)(tap) 2 RuORu(tap) 2 (H 2 O)] 2 + {tap=2-(m-tolylazo)pyridine} ion by three glycine-containing dipeptides in aqueous medium at physiological pH

The interaction of the title complex with selected glycine-containing dipeptides(L-L′H) such as glycyl-glycine(L-L1H), glycyl-L-alanine (L-L2H) and glycyl-L-leucine(L-L3H) has been studied spectrophotometrically in aqueous medium as a function of [substrate complex], [ligand] and temperature. The reaction has been monitored at 600 nm where the spectral difference between the reactant and product is a maximum. At pH 7.4, the interaction with studied dipeptides shows two parallel steps. i.e., it shows a non-linear dependence on the concentration of dipeptides; both processes are ligand-dependent. The rate constants for the processes are: k1 ~10 − 3 s − 1 and k 2 ~10 − 5 s − 1. The activation parameters were calculated from Eyring plots. Based on the kinetic and activation parameters an associative interchange mechanism is proposed for the interaction processes. From the temperature dependence of the outer sphere association equilibrium constant, the thermodynamic parameters were also calculated. The product of the reaction has been characterized by IR and ESI-mass spectroscopic analysis. The kinetics of the interaction between [(H2O)(tap)2RuORu(tap)2(H2O)]2+ {tap=2-(m-tolylazo)pyridine} ion and glycine-containing dipeptides such as glycyl-glycine, glycyl-L-alanine and glycyl-L-leucine has been studied spectrophotometrically in aqueous medium as a function of nucleophile concentration, temperature and pH at constant ionic strength. The rate and activation parameters, ESI-mass spectra and IR data were used to deduce a plausible mechanism.

Kinetic Study of the Interaction of Three Glycine-Containing Dipeptides with Hydroxopentaaquarhodium(III) Ion in Aqueous Medium

The kinetics of the interaction of three glycine-containing dipeptides, namely, glycyl-L-valine (L1-L′H), glycyl-glycine (L2-L′H) and glycyl-L-glutamine (L3-L′H), with [Rh(H2O)5OH]2+ has been studied spectrophotometrically in aqueous medium as a function of the Rh(H2O)5OH2+ and dipeptide concentrations, pH and temperature, at constant ionic strength. At pH = 4.3, the substrate complex exists predominantly as the hydroxopentaaqua species and dipeptides as zwitterions. The reaction has been found to proceed via two parallel paths: both processes are ligand dependent. The rate constants for the processes are of the order: k1∼10−3 s−1 and k2∼10−5 s−1. The activation parameters for both steps were evaluated from Eyring plots. Based on the kinetic and activation parameters an associative interchange mechanism is proposed for both of the interaction processes. The low \(\Delta H_{1}^{\neq}\) and \(\Delta H_{2}^{\neq}\) values and large negative values of \(\Delta S_{1}^{\neq}\) and \(\Delta S_{2}^{\neq}\) support the associative mode of activation for both processes. The product of the reaction has been characterized using IR and ESI-mass spectroscopic analysis.

Kinetic study of the interaction of three glycine-containing dipeptides with diaquaethylenediamineplatinum(II) in aqueous medium

The kinetics of the interaction of three glycine-containing dipeptides, namely, glycine-L-leucine (Gly-Leu), glycine-L-isoleucine (Gly-Ile), and glycine-valine (Gly-Val) with [Pt(en)(H2O)2](ClO4)2 has been studied spectrophotometrically as a function of [substrate complex], [dipeptides] and temperature at a particular pH(4.0), where the substrate complex exists predominantly as the diaqua species and the dipeptides as a zwitterion. The substitution reaction shows two consecutive steps; the first is the ligand-assisted anation and the second is the chelation step. The activation parameters for both the steps were evaluated using Eyring's equation. The low ΔH1≠ and large negative value of ΔS1≠ as well as ΔH2≠ and ΔS2≠ indicate an associative mode of activation for both the aqua ligand substitution processes. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43: 498–506, 2011

Solvation and Hydrogen Bonding in Alanine- and Glycine-Containing Dipeptides Probed Using Solution- and Solid-State NMR Spectroscopy

The NMR chemical shift is a sensitive reporter of peptide secondary structure and its solvation environment, and it is potentially rich with information about both backbone dihedral angles and hydrogen bonding. We report results from solution- and solid-state (13)C and (15)N NMR studies of four zwitterionic model dipeptides, L-alanyl-L-alanine, L-alanyl-glycine, glycyl-L-alanine, and glycyl-glycine, in which we attempt to isolate structural and environmental contributions to the chemical shift. We have mapped hydrogen-bonding patterns in the crystalline states of these dipeptides using the published crystal structures and correlated them with (13)C and (15)N magic angle spinning chemical shift data. To aid in the interpretation of the solvated chemical shifts, we performed ab initio quantum chemical calculations to determine the low-energy conformers and their chemical shifts. Assuming low energy barriers to interconversion between thermally accessible conformers, we compare the Boltzmann-averaged chemical shifts with the experimentally determined solvated-state shifts. The results allow us to correlate the observed differences in chemical shifts between the crystalline and solvated states to changes in conformation and hydrogen bonding that occur upon solvation.

Binding of proline- and hydroxyproline-containing peptides and proteins to the capillary wall

Sticking of peptides (as demonstrated by peak distortion) containing a high proportion of glycine and proline residues to the capillary wall was investigated. At acid pH where the carboxy terminal proline (e.g. Gly–Pro) is protonated, distinct sticking of these peptides occurred. On the contrary, the Pro–Gly peptide yielded a well shaped peak. At alkaline pH, where the situation was reversed, the peptide sticking most to the wall was Gly–Gly, while the behaviour of the dipeptides possessing N- or C-terminal proline did not suffer from sticking to the wall. It was concluded that the separation of simple proline- and glycine-containing dipeptides can be partly optimized by manipulating the pH of the background electrolyte; particularly if cetyltrimethylammonium bromide, methanol or acetonitrile is added to the run buffer (reversed polarity mode with cetyltrimethylammonium bromide). However, all attempts to resolve more complex mixtures of proline- (and hydroxyproline-) containing di- and tripeptides failed; addition of an organic modifier, i.e. methanol and acetonitrile, hexylamine, triethylamine and cetyltrimethylammonium bromide was unsuccessful. Such separations can be materialized by using simple 25 mmol/l phosphate buffer at pH 10.5 provided that the sample is dissolved in (aqueous) 17.5 mmol/l Brij or 33 mmol/l sodium dodecyl sulfate. These systems are also applicable to large polypeptides rich in proline, hydroxyproline and glycine: typically parent collagen α-chains, their dimers, trimers and higher polymers were successfully separated.

Use of dipeptides for the synthesis of glutathione by astroglia-rich primary cultures.

The intracellular content of glutathione in astroglia-rich primary cultures derived from the brains of newborn rats was used as an indicator for the ability of these cells to use dipeptides for glutathione synthesis. For restoration of the glutathione level, after a 24-h starvation period in the absence of glucose and amino acids, glucose, glutamate, cysteine, and glycine have to be present in the incubation buffer. The dipeptides CysGly and gammaGluCys were able to substitute for cysteine plus glycine and glutamate plus cysteine, respectively. Half-maximal contents of glutathione were found at 20 microM CysGly and 3 mM gammaGluCys. In addition, the oxidized forms of the dipeptides CysGly and GlyCys could replace cysteine plus glycine for glutathione restoration, and the glycine-containing dipeptides GlyGly, GlyLeu, GlyGlu, GlyGln, and gammaGluGly could partially substitute for the glycine necessary for the replenishment of glutathione. The glutathione resynthesis in the presence of CysGly plus glutamate was totally inhibited in the presence of buthionine sulfoximine, an inhibitor of gamma-glutamylcysteine synthetase. In contrast, glutathione restoration from gammaGluCys at a concentration of 10 mM in the presence of glycine was not influenced by the inhibitor. The use of CysGly or gammaGluCys was not affected by the presence of the dipeptidase inhibitors cilastatin or bestatin. In addition, carnosine and several other dipeptides applied in a 50-fold excess only slightly prevented the use of CysGly, hinting at the existence in astroglial cells of a transport system specific for CysGly. The results demonstrate that astroglial cells can use dipeptides for intracellular glutathione synthesis and that the dipeptides most likely are taken up as intact molecules into astroglial cells before intracellular hydrolysis occurs.

Purification and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis.

Porphyromonas gingivalis, a Gram-negative anaerobic rod, has been closely associated with the initiation and progression of periodontal disease. This organism has been shown to produce a large number of proteolytic enzymes which can degrade a variety of tissue proteins, and these are considered to be major virulence factors. One of the proteinases produced by this organism, referred to as gingipain-1, has been purified to homogeneity from P. gingivalis culture medium by a combination of gel filtration and ion-exchange chromatography. The enzyme was found to have a molecular mass near 50 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a pH optimum in the neutral to alkaline range, and a requirement for cysteine for activation and Ca2+ for stabilization. Amino-terminal sequence analysis indicated that gingipain belongs to a new, so far unknown, subfamily of cysteine proteinases. Three unusual features of this proteinase are: (a) the stimulation of amidolytic activity by glycine-containing dipeptides; (b) a narrow specificity which is limited to peptide bonds containing arginine residues; and (c) resistance to inhibition by proteinase inhibitors in human plasma.

Characterization and regional distribution of strychnine-insensitive [ 3H]glycine binding sites in rat brain by quantitative receptor autoradiography

Recent evidence suggests that a strychnine-insensitive glycine modulatory site is associated with the N-methyl- d-aspartate receptor-channel complex. A quantitative autoradiographic method was used to characterize the pharmacological specificity and anatomical distribution of strychnine-insensitive [ 3H]glycine binding sites in rat brain. [ 3H]Glycine binding was specific, saturable, reversible, pH and temperature-sensitive and of high affinity. [ 3H]Glycine interacted with a single population of sites having a K D of approximately 200 nM and a maximum density of 6.2 pmol/mg protein (stratum radiatum, CA1). Binding exhibited a pharmacological profile similar to the physiologically defined strychnine-insensitive glycine modulatory site. Binding was stereoselective; the rank order of potency of simple amino acids as displacers of binding was: glycine > d-serine > d-alanine > l-serine > l-alanine > l-valine > d-valine. Binding was not altered by the inhibitory glycine receptor ligand, strychnine, by the glutamate agonists, quisqualate and kainate, or by GABA receptor selective ligands. Most competitive agonists or antagonists of the N-methyl- d-aspartate recognition site were ineffective displacers of glycine binding. The exceptions were the aminophosphono series of antagonists, d-alpha-aminoadipate, gamma- d-glutamylglycine and beta- d-aspartylaminomethylphosphonic acid. However, the inhibition of [ 3H]glycine binding produced by the aminophosphono compounds could be accounted for by the level of glycine contamination present in these compounds. The non-competitive NMDA receptor-channel blockers, phencyclidine, its thienyl derivative, and MK-801 did not alter glycine binding. Kynurenate, glycine methylester, l-serine-O-sulfate , l-homocysteic acid, and several glycine-containing dipeptides were effective displacers of glycine binding. Structure-activity relations of agonists and antagonists of the strychnine-insensitive glycine binding site are discussed. The distribution of strychnine-insensitive [ 3H]glycine binding was heterogeneous with the following rank order of binding densities: hippocampus > cerebral cortex > caudate-putamen ⩾ thalamus > cerebellum > brain stem. This distribution of binding was correlated with N-methyl- d-aspartate-sensitive [ 3H]glutamate binding ( r 2 = 0.77; P< 0.001; Pearson product-moment) and [ 3H]thienylcyclohexylpiperidine binding ( r 2 = 0.72; P < 0.001 ). These observations are consistent with the hypothesis that the strychnine-insensitive glycine binding site is closely associated with the N-methyl- d-aspartate receptor-channel complex. These data also suggest that the stoichiometry between these binding sites is approximately 1:3:4 (thienylcyclohexylpiperidine: glycine:glutamate) in stratum radiatum of area CA1. However, in other brain regions, there were more glycine than glutamate binding sites suggesting that there may be heterogeneity in the N-methyl- d-aspartate receptor-channel complex.

L-leucine and its analogue: Specific inhibitors for S-benzyl-L-cysteine- p-nitroanilide-hydrolyzing enzyme in Escherichia coli B

An enzyme that catalyzes hydrolysis of S-benzyl-L-cysteine-p-nitroanilide was purified from E. coli B. The enzyme was a monomer with a molecular weight of 82,000. In addition to L-cysteinylglycine, the enzyme hydrolyzed various glycine-containing dipeptides most efficiently at pH 7.0. The enzyme required no metal ions for activity and was specifically inhibited by L-leucine and its analogue with free carboxyl group at the physiological concentrations.

ChemInform Abstract: N‐METHYL PEPTIDES. VI. INFLUENCE OF N‐METHYLATION ON THE CRYSTAL STRUCTURES OF THREE GLYCINE‐CONTAINING DIPEPTIDES

Chemischer InformationsdienstVolume 15, Issue 41 Physical Organic Chemistry ChemInform Abstract: N-METHYL PEPTIDES. VI. INFLUENCE OF N-METHYLATION ON THE CRYSTAL STRUCTURES OF THREE GLYCINE-CONTAINING DIPEPTIDES A. AUBRY, A. AUBRYSearch for more papers by this authorB. VITOUX, B. VITOUXSearch for more papers by this authorM. MARRAUD, M. MARRAUDSearch for more papers by this author A. AUBRY, A. AUBRYSearch for more papers by this authorB. VITOUX, B. VITOUXSearch for more papers by this authorM. MARRAUD, M. MARRAUDSearch for more papers by this author First published: October 9, 1984 https://doi.org/10.1002/chin.198441079Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume15, Issue41October 9, 1984 RelatedInformation

Peptide kinetics. Part 12.—The effect of Zn(II) on the reaction of some glycine-containing dipeptides and substituted diketopiperazines at pH 5.6 and 368.2 K

The kinetics of the simultaneous reactions of sequence inversion of a dipeptide pair AB, BA through the diketopiperazine intermediate [graphic omitted] and hydrolysis of the dipeptide pair to give amino acids A and B have been investigated for the following systems: glycyl-L-leucine, L-leucyl-glycine, glycyl-L-leucine diketopiperazine; glycyl-L-alanine, L-alanyl-glycine, glycine-L-alanine diketopiperazine; glycyl-glycine and glycyl-glycine diketopiperazine at pH 5.6 and 368.2 K in the presence and absence of Zn(II) ions. Zn(II) ions catalyze all the reactions involved including the formation of the diketopiperazines and their cleavage. Suggestions are made concerning the role of the Zn(II) ions in these reactions.

The Role of Dipeptidases in Cells of Escherichia coli Strain K-12

Abstract To obtain further information about the role of bacterial peptidases in vivo, the enzymic activity of Escherichia coli strain K-12 was studied. The substrates were four glycine-containing dipeptides in which the other amino acid was either l-leucine or l-phenylalanine, and the bacteria were harvested from cultures that varied in age from 24 hours (young cultures) to 144 hours (fully aged cultures). The specific enzymic activity of broken cell preparations toward a given substrate remains constant regardless of the age of the bacterial culture, but the relative activity (measured under the same conditions) increases in the following order: glycylleucine, glycylphenylalanine, leucylglycine, phenylalanylglycine. On the other hand, intact cells from young cultures show equal specific activity for the four substrates. This activity decreases in parallel during aging of the cultures, reaching a minimal level in about 72 hours when the pH of the culture is allowed to fall below about 6.0; at pH values nearer neutrality, the decrease in activity is less complete and occurs less rapidly. The peptidase activity of whole cell preparations is comparable to that of broken cell preparations only with glycylleucine as substrate; even with this substrate full enzymic activity is seen only with intact bacteria from young cultures. The enzymic activity of intact bacteria toward the other substrates represents only a fraction of the activity observed in broken cell preparations. The significance of these results is discussed, and it is concluded that the low specific activity of resting cells is not explicable in terms of the differential permeability of bacteria to the dipeptides.

Coördination Complexes and Catalytic Properties of Proteins and Related Substances. IV. Reactions of Glycine-containing Dipeptides with Cupric Ions and with p-Nitrophenyl Acetate1

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCoördination Complexes and Catalytic Properties of Proteins and Related Substances. IV. Reactions of Glycine-containing Dipeptides with Cupric Ions and with p-Nitrophenyl Acetate1Walter L. Koltun, Melvin Fried, and Frank R. N. GurdCite this: J. Am. Chem. Soc. 1960, 82, 1, 233–241Publication Date (Print):January 1, 1960Publication History Published online1 May 2002Published inissue 1 January 1960https://doi.org/10.1021/ja01486a052RIGHTS & PERMISSIONSArticle Views77Altmetric-Citations80LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1020 KB) Get e-Alerts Get e-Alerts