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At least 523 records · Page 29Linked to original sources
PubMed1996

Identification of a novel endogenous memory facilitating cyclic dipeptide cyclo-prolylglycine in rat brain.

Using high-performance liquid chromatography, gas-chromatography and chromato-mass spectrometry methods a novel endogenous cyclic dipeptide cyclo-prolylglycine was identified in rat brain. Its content according to gas chromatography is 2.8 +/- 0.3 nmol/g wet brain. Synthetic cyclo-prolylglycine has demonstrated antiamnesic activity in the passive avoidance test in rats at a dose of 0.1 mg/kg i.p. Cyclic dipeptide cyclo-prolylglycine seems to be a memory facilitating substance and its presence in rat brain suggests the existence of a new mechanism of memory regulation.

Animals↗
PubMed1996

Dmt-Tic-OH a highly selective and potent delta-opioid dipeptide receptor antagonist after systemic administration in the mouse.

Dmt-Tic-OH (DTOH) and Dmt-Tic-Ala-OH (DTAOH), effective antagonists in vitro, represent a new potent opioid dipeptides for the delta-opioid receptor (Ki delta of 0.022 nM and a selectivity, Ki mu/Ki delta, of 150,000 for DTOH; Ki delta of 0.285 nM and a selectivity Ki mu/Ki delta, of 20,4 for DTAOH). In the present study we considered the pharmacological activity of these two new delta opioid peptide receptor antagonists in vivo. Therefore, we have evaluated their possible antagonistic activity against the antinociception induced by the highly selective delta opioid receptor agonist, [D-Ala2]deltorphin II (DEL). Furthermore, these two delta opioid peptide receptor antagonists were injected centrally or peripherally in order to assess their ability to act also after systemic administration. Concurrent i.c.v. injection of DTOH or DTAOH (0.5-1.0-2.0 nM) with DEL (5 nmol) induced a significant reduction of DEL antinociception. By contrast, while DTOH (10-20-40 mg/kg) administered peripherally (i.p., s.c. or i.v.) was also able to reduce DEL antinociception, DTAOH failed. The present results indicate that DTOH is the first opioid dipeptide with delta antagonist activity after systemic administration and it could be important in the clinical and therapeutic applications.

Animals↗
PubMed1989

Influence of molecular structure and plasma hydrolysis on the metabolism of glutamine-containing dipeptides in humans.

Glutamine-containing dipeptides may serve as a source of glutamine in parenteral nutrition solutions. To study the metabolism of glycyl-L-glutamine (gly-gln) and L-alanyl-L-glutamine (ala-gln) bolus injections of both dipeptides (0.1 mmol/kg within 40 seconds) were performed in five healthy male volunteers. Furthermore, plasma hydrolase activity against both peptides was tested by in vitro incubation. Both peptides were rapidly cleared from plasma after injection; however clearance was significantly greater for ala-gln than for gly-gln (1,595 +/- 124 v 507 +/- 14 mL/min). Arterial concentrations of constituent amino acids rose after peptide injection, indicating hydrolysis of the peptides. Glutamine concentration, for example, rose from 573 +/- 29 to a maximum of 718 +/- 34 mumol/L after gly-gln and from 570 +/- 15 to 900 +/- 53 mumol/L after ala-gln injection. Both peptides were hydrolyzed by plasma hydrolases during in vitro incubation. Hydrolysis was greater for ala-gln than for gly-gln. Half-lives of ala-gln and gly-gln were 46 +/- 3 and 553 +/- 160 minutes, respectively. For both peptides, plasma hydrolysis was too low to contribute significantly to in vivo clearance. Our results indicate that gly-gln and ala-gln are suitable sources for glutamine in parenteral nutrition solutions. Furthermore, plasma hydrolases do not play a significant role in peptide metabolism. Both peptides therefore appear to be primarily metabolized via extracellular hydrolysis, presumably by hydrolases on the cell membranes and consecutive uptake of the liberated amino acid residues.

Adult↗
PubMed1990

The histidine-containing dipeptides, carnosine and anserine: distribution, properties and biological significance.

The biological significance of histidine-containing dipeptides discovered within the composition of nitrogenous extracts of skeletal muscles at the beginning of this century is still open to question. The present investigation is concerned with the analysis of distribution and metabolism of these compounds with special reference to their effects on functional activity of membrane-linked enzymatic systems, stability of cellular membranes, muscle contractibility, etc. The proposed hypothesis on stabilizing properties of carnosine and related substances on biological membranes is based on the ability of the dipeptides to interact with lipid peroxidation products and active oxygen species and to prevent membrane damage. This remarkable antioxidative effect of carnosine reflects the high therapeutic value of this compound as an anti-inflammatory drug and a prominent tool in wound healing.

Alanine↗
PubMed1994

Dipeptide synthesis and separation in a reversed micellar membrane reactor.

The synthesis of dipeptide AcPheLeuNH2 catalyzed by alpha-chymotrypsin encapsulated in TTAB/octanol/heptane reversed micelles was investigated in a tubular ceramic membrane reactor, operated in a batch mode. The reaction medium conditions (TTAB concentration, buffer molarity, and pH) were optimized using a factorial design in order to achieve maximum synthesis rates. Hydrated reversed micelles permeated through the membrane together with the substrate ester, dipeptide, and by-products. However, as a result of the low solubility of the peptide in the reaction medium, selective precipitation occurred, thus enabling the complete retention of the solid product by the ultrafiltration membrane and therefore an integration of a separation step in the biotransformation process. In spite of the continuous accumulation of solids inside the reactor, constant permeation flow rates could be maintained throughout the operation. The influence of alpha-chymotrypsin, TTAB, and water concentration on the kinetics and mass transfer of the system was also investigated. The behavior of the system during a continuous experiment was also evaluated.

Biotechnology↗
PubMed1991

Coordination of copper(II) ions to catechoyl-dipeptides, the inhibitors of leucine aminopeptidase and ribonucleotide reductase.

Potentiometric and spectroscopic study of the coordination ability of 2,3- and 3,4-dihydroxybenzoyl-dipeptides has shown that catechoyl-dipeptides are very strongly-binding ligands. The coordination begins at the catechol site at pH below 4. In the case of 2,3-dihydroxy derivatives the peptide unit may also be involved in the copper(II) ion coordination via its peptide nitrogens. The biological tests have indicated that the studies ligands may be effective inhibitors of ribonucleotide reductase in some cases, with a reasonable level of selectivity.

Animals↗
PubMed1994

Glutamine-based dipeptides are utilized in mammalian cell culture by extracellular hydrolysis catalyzed by a specific peptidase.

A murine hybridoma (CC9C10) was grown in media containing alanyl-glutamine (ala-gln) or glycyl-glutamine (gly-gln) as a substitute for glutamine. High cell yields were obtained in the presence of 6 mM ala-gln or 20 mM gly-gln. The final cell yield in gly-gln was 14% higher than in gln. Monoclonal antibody productivity was comparable in gln, ala-gln or gly-gln. Substrate utilisation and metabolism was affected by the presence of the dipeptides, particularly with gly-gln. The specific consumption rates of glucose and six amino acids were reduced. Also the accumulation of ammonia and lactate was significantly lower. The higher concentration of gly-gln was necessary for cell growth because of the presence of a peptidase with a lower affinity for gly-gln. The peptidase activity of the basal medium and serum was low. However, a substantial peptidase activity was found in the cytosolic fraction of the cells with an apparent Km of 1.2 mM with respect to ala-gln and 14 mM with respect to gly-gln. It is proposed that the mechanism of dipeptide utilisation involves extracellular hydrolysis by this peptidase following its release into the culture medium.

Amino Acids↗
PubMed1989

The dipeptide Lys-Pro restores the diminished wound healing following treatment with anti-T-helper cell monoclonal antibody.

To determine the role of T-cell subsets in wound healing, we studied the granulation tissue proliferation after depletion of CD4 or CD8 positive cells. Granulation tissue proliferation in CD8-diminished AB mice was significantly higher than in the control group as a result of depleted suppressor cell activity. The CD4-depleted mice produced granulation tissue in less than 30% of the control group. To investigate the role of dipeptidylpeptidase IV on CD4 positive cells in wound healing we used Lys-[Z(NO2)]-Pro, a chemically modified dipeptide which may result by degradation of polypeptides by this peptidase. It was possible to restore the diminished capability of granulation tissue proliferation in CD4-depleted mice by a single treatment with the dipeptide Lys-[Z(NO2)]-Pro. Our results suggest that: (i) the CD4 positive T-helper subset regulates wound healing, and (ii) products of degradation by dipeptidylpeptidase IV may bypass T-helper cell function.

Animals↗
PubMedDate not supplied

The dipeptide Lys-Pro attenuates interleukin-1 beta-induced anorexia.

The carboxyl-terminal tripeptide of alpha-MSH(1-13), Lys-Pro-Val, antagonizes anorexia induced by interleukin-1 beta (IL-1). The present studies were undertaken to determine if the Lys-Pro dipeptide portion of this tripeptide likewise antagonizes anorexia induced by ICV administration of 0.5 pmol IL-1 in rats previously deprived of food. This dose of Lys-Pro did significantly attenuate the IL-1-induced anorexia, but only for 1 h after infusion. Simultaneous administration of a larger dose (5.0 pmol) of Lys-Pro reversed the IL-1-induced anorexia during both the 0-1-h and 2-4-h periods. In addition, both 0.5 and 5.0 pmol of the D-substitute tripeptide, Lys-D-Pro-Thr (LDPT), similarly attenuated the IL-1-induced anorexia. The ICV administration of 5.0 pmol Lys-Pro also did not have any significant effects on food consumption. These results indicate that the dipeptide Lys-Pro may have a short-term antagonistic action against the anorexia induced by IL-1, and it is possible that this action may be partially mediated by the blockade of IL-1 on its own receptor.

Amino Acid Sequence↗
PubMed1990

Effect of immunomodulator adamantylamide dipeptide on antibody response to influenza subunit vaccines and protection against aerosol influenza infection.

Adamantylamide dipeptide (AdDP) is a novel synthetic compound combining the antiviral properties of amantadine and the essential adjuvant activity of immunomodulator muramyl dipeptide. Mice were immunized with influenza A/Taiwan/1/86 (H1N1), A/Sichuan/2/87 (H3N2) and influenza B/Beijing/1/87 subunit vaccines containing AdDP or aluminium hydroxide (Al(OH)3). Induction of homologous haemagglutination-inhibition (HI) antibodies and correlation to protection against lethal aerosol influenza A/PR/8/34 (H1N1) infection were investigated. Subunit vaccine containing A/Sichuan (H3N2) and Al(OH)3 stimulated high HI antibody titres but failed to provide protection against heterologous influenza A (H1N1) challenge infection following either the primary or the secondary immunizations. In contrast, similar treatment with A/Sichuan subunit vaccine containing AdDP conferred significant protection against heterologous challenge despite low levels of circulating antibody. Primary immunization with even influenza B/Beijing subunit vaccine containing AdDP, but not Al(OH)3, provided partial protection against influenza A challenge. These results suggest that appropriate immunomodulators like AdDP can convert restricted homotypic immunity induced by inactivated influenza subunit vaccines to advantageous cross-reacting type of heterologous response.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Kinetics and mechanism for the conformational transition in p-guanidinobenzoate bovine trypsinogen induced by the isoleucine-valine dipeptide.

The interaction between p-guanidinobenzoate-trypsinogen and the isoleucine-valine dipeptide has been investigated by temperature-jump relaxation spectrometry. Using the absorbance at 281 nm the concentration dependence of the relaxation parameters is consistent with the conventional induced-fit model: rapid ligand binding coupled to a slower intramolecular change; some alternative mechanisms can be excluded. At 296 K, 0.1 M Tris HCl, pH = 7.4, the dissociation equilibrium constant for the overall process is K = 5.1(+/- 0.2) X 10(-5) M; for the binding step K1 = 2.3(+/- 0.3) X 10(-3) M and the rate constants for the structural change are k2 = 26(+/-6)s-1 and k-2 = 0.61(+/- 0.04)s-1; the overall dissociation reaction enthalpy is delta H0 = 26(+/-6)KJmol-1 and the reactiom entropy is delta S0 = 4(+/- 20) kJ-1 mol-1. In combination with CD and X-ray crystallographic data, the results of this study suggest that the binding of the dipeptide to a trypsinogen-like, partially disordered conformation induces a transition to a trypsin-like highly ordered structure.

Animals↗
PubMed1992

Histidine dipeptide levels in ageing and hypertensive rat skeletal and cardiac muscles.

1. In rat skeletal muscles (longissimus dorsi and quadriceps femoris), carnosine and anserine levels decreased 35-50% during senescence, and were 35-45% lower in hypertensive rats compared to normotensive levels. 2. In rat left ventricular cardiac muscle, although no free carnosine and anserine were detected, the total level of histidine dipeptides declined 22% during senescence and in hypertensive animals decreased 35% compared to normotensive levels. 3. The significance of these changes in relation to the possible antioxidant roles of histidine dipeptides in muscle is discussed.

Aging↗
PubMed1984

Structure-activity relations of dipeptide antagonists of excitatory amino acids.

Structure-activity relations of dipeptides related to gamma-D-glutamylglycine have been investigated with respect to the ability of these substances to antagonize depolarizing responses of frog motoneurones in vitro to N-methyl-D-aspartate, kainate and quisqualate. A terminal phosphono group was optimal for N-methyl-D-aspartate antagonist activity in relation to both potency and selectivity. Substances containing a terminal phosphono group were relatively poor antagonists of kainate or quisqualate responses. Terminal carboxylic and sulphonic groups were both effective with respect to kainate and/or quisqualate antagonism. Sulphonic compounds were the more selective in this type of action because of their low affinity for N-methyl-D-aspartate receptors. Optimum chain length for N-methyl-D-aspartate antagonism was between one and two carbon atoms shorter than for optimum kainate/quisqualate antagonist activity. Bulky groups within the N-acylated amino acid moiety generally, but differentially, reduced the ability of the substance to antagonize responses to each of the three agonists. Glutamyl peptides were generally more effective than aspartyl peptides of the same overall chain length. However, the most potent dipeptide (selective for N-methyl-D-aspartate antagonism) was the aspartyl derivative, beta-D-aspartylaminomethyl phosphonate, for which there was no glutamyl equivalent. Other useful substances to emerge from this study include the relatively selective kainate/quisqualate antagonists, gamma-D-glutamylaminomethyl sulphonate and gamma-D-glutamyltaurine. If similar selectivity is shown in other preparations also, these substances may prove preferable to gamma-D-glutamylglycine as antagonists of synaptic excitation mediated by kainate or quisqualate receptors.

Amino Acids↗
PubMed1994

Femtomole detection of amino acids and dipeptides by gas chromatography-negative-ion chemical ionization mass spectrometry following alkylation with pentafluorobenzyl bromide.

Amino acids and di- and tripeptides were derivatized by extractive alkylation using pentafluorobenzyl bromide (PFBBr) followed by reaction with heptafluorobutyric anhydride (HFBA) and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA). Good chromatographic separation and the formation of intense diagnostic ions were observed for the derivative when examined using gas chromatography-negative-ion chemical ionization mass spectrometry (GC-NICI-MS). Of the 20 amino acids investigated, only Arg and Glu could not be detected by this method. Also, dipeptides which included neutral amino acid residues were derivatized with more success than those containing either acidic or basic residues. Each of the amino acids or dipeptides formed one major derivative with the exception of Asn which formed two derivatives with either one or two HFB groups. This derivatization method was optimized with respect to the reaction temperature, reaction time, and choice of derivatizing reagents. Recoveries of derivatized [3H]-labeled Phe, Lys, and Thr were 76, 55, and 34%, respectively. Linearity was observed from 10 to 2000 pg of Ala per vial; selected-ion monitoring provided a detection limit of less than 150 fg with a signal-to-noise (S/N) ratio of 80 to 1. This method has proven to work well with urine samples and shows great promise for the detection of small peptides at low levels.

Acylation↗
PubMed1990

Contribution of the C-terminal dipeptide of transforming growth factor-alpha to its activity: biochemical and pharmacologic profiles.

We have used a matrix of biological (two distinct guinea-pig stomach contractile smooth muscle preparations) and biochemical (human placental membrane receptor binding and phosphorylation) assays to evaluate the activity profiles of epidermal growth factor-urogastrone (EGF-URO, mouse and human), transforming growth factor-alpha (TGF-alpha, human) and the TGF-alpha derivative lacking the C-terminal dipeptide, Leu49-Ala50, TGF-alpha-(1-48). In the longitudinal muscle (LM) bioassay, the relative potencies of the peptides were: EGF-URO greater than TGF-alpha greater than TGF-alpha-(1-48), with relative activity ratios (EC50S) of approximately 1:3:16. In the LM assay system, TGF-alpha-(1-48) was a partial agonist. In the circular muscle (CM) bioassay, the relative order of potencies was: TGF-alpha- greater than EGF-URO greater than TGF-alpha-(1-48), with EC50S of about 1:2:7. In the CM assay, all three peptides were full agonists, even though EGF-URO caused an intense desensitization of the tissue whereas TGF-alpha and TGF-alpha-(1-48) did not. The relative affinities of the peptides in the placenta membrane binding assay, EGF-URO greater than TGF-alpha greater than TGF-alpha-(1-48), were in good qualitative and quantitative agreement with the LM (but not the CM) bioassay, with relative KDS in the proportions of about 1:3:17. In the phosphorylation assay, using either the phosphorylated EGF-URO receptor or calpactin-II as an index of receptor kinase activation, the relative potencies of the peptides, EGF-URO greater than TGF-alpha greater than TGF-alpha-(1-48), were also qualitatively in accord with the relative potencies measured in the LM and ligand binding assays (but not in the CM preparation); however, quantitatively, the relative potency ratios (EC50S) observed in the phosphorylation assay (1:2:3) were somewhat out of keeping with the relative values observed in the LM and ligand binding assays. All three peptides were full agonists in the phosphorylation assay. Our data point to the importance of the C-terminal dipeptide, Leu49-Ala50 of TGF-alpha in terms of the binding affinity and intrinsic activity of this polypeptide; and our work provides further evidence for the distinct nature of the EGF-URO/TGF-alpha receptor system present in the CM bioassay preparation. The biological/biochemical activity profiles documented for the three polypeptides can serve as a basis for the further evaluation of other synthetic and naturally occurring members of the EGF-URO/TGF-alpha family of polypeptides.

Animals↗
PubMed1985

An in vitro system to measure gene expression based on dipeptide synthesis.

A simplified E. coli in vitro system has been developed to study gene expression based on the synthesis of the first di- or tripeptide of the gene product. Plasmids containing bacterial and chloroplast genes have been used as templates in this system. The expression of the E. coli L10 operon, which is under both transcriptional and translational control, has been investigated in some detail using the dipeptide system. A similar system has been developed, using eukaryotic translation components, to measure the expression of eukaryotic mRNA based on dipeptide formation.

Animals↗