Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “dipeptides”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMed1990

Synthesis of the alpha and beta anomer of an N-triglycosyl dipeptide.

O-alpha-D-Glucopyranosyl-(1----6)-O-beta-D-glucopyranosyl-(1----6)-1-N- [L-aspart-1-oyl-(L-proline)-4-oyl]-alpha- and -beta-D-glucopyranosylamine have been prepared, as models for a derivative possibly present in the glomerular basement membrane of rats, by condensation of the corresponding D-glucosyl-dipeptide derivatives with 2,3,4,2',3',4',6'-hepta-O-acetyl-alpha-D-isomaltopyranosyl bromide in the presence of mercuric cyanide, followed by deprotection of the trisaccharide-dipeptide derivatives.

Amino Acid Sequence↗
PubMed1984

Leishmania tropica: protective response in C3H mice vaccinated with excreted factor crosslinked with the synthetic adjuvant, muramyl dipeptide.

Excreted factor, an immunosuppressive, acidic polysaccharide released by promastigotes of Leishmania tropica major in culture, was chemically crosslinked to the synthetic adjuvant muramyl dipeptide via the bifunctional imidoester dimethyladipimidate and poly-L-lysine. This conjugate, an uncrosslinked mixture of the components, or each of the components alone were injected one to three times into different groups of 8- to 12-week-old C3H mice. The mice were challenged 2 weeks after the last injection with 2 X 10(6) promastigotes of L. t. major in the base of the tail. For the next 5 weeks, the animals were monitored for number of parasites and size of the lesion which developed at the site of the challenge. Mice receiving one intraperitoneal injection of the conjugate were partially protected against challenge. Treated animals had higher initial parasite numbers but showed a more rapid clearing of the parasites. Furthermore, the treated animals developed smaller lesions that healed quicker than did those of the control groups. Multiple injections, or injection into a footpad, rather than intraperitoneally, reduced the ability to elicit a protective response. On the other hand, muramyl dipeptide injected into a footpad was partially protective. Antibody production to excreted factor, which was measured by indirect hemagglutination of sensitized erythrocytes, was detected after challenge in mice which had received conjugate or conjugate components. A delayed hypersensitivity reaction (measured by skin testing) was not detected in any of the groups prior to challenge.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

Enhancement in anti-Semliki Forest virus activity of ds RNA by a muramyl dipeptide.

Antiviral activity of an interferon-inducing mycoviral ds RNA against Semliki Forest virus infection was considerably enhanced by N-palmitoylmuramyl-L-alanyl-D-isoglutamine (PMDP), a new muramyl dipeptide. This enhancement in activity was not due to increased production of interferon, but resulted probably from a PMDP-induced increase in nonspecific resistance to infection. These results indicate that a combined treatment with an interferon inducer and muramyl dipeptide may prove highly useful to control effectively viral infections.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Microiontophoretic application of muramyl-dipeptide upon single cortical, hippocampal and hypothalamic neurons in rats.

Muramyl-dipeptide (MDP), a metabolite of bacterial cell walls, has a variety of biological effects, including the induction of acute phase serum glycoproteins and fever, and the promotion of slow wave sleep. Muramyl-dipeptide and other products, derived from immune responses, may act directly in the CNS to recruit secondary autonomic and endocrine responses to disease. To test this hypothesis the properties of single neuron discharges, following local application (microiontophoresis) of MDP within the somatosensory cortex, the dorsal hippocampus and the medial basal hypothalamus were studied in rats. The results obtained from cortical (N = 30), hippocampal (N = 28) and hypothalamic (N = 32) neurons demonstrated a direct effect of MDP upon all three regions of the brain. In addition, MDP modified the responses of these same neurons to morphine. These results support a role of MDP in the process of neuro-immune modulation and further demonstrate an interaction between lymphoid agents and opioids in the CNS.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Further analysis of the short-term inhibition of food intake in humans by the dipeptide L-aspartyl-L-phenylalanine methyl ester (aspartame).

It was reported previously that the dipeptide sweetener aspartame suppresses food intake in humans by a postingestive action. The present study examined the hypothesis that this is due to an effect of phenylalanine, one of the primary breakdown products of aspartame (phenylalanine is a potent releaser of the so-called satiety hormone cholecystokinin, CCK). Capsulated aspartame (400 mg) administered to human volunteers reduced food intake by 15% (253 kcal) in a lunchtime test meal begun 1 hour later. However, neither phenylalanine (200 mg) nor the other constituent amino acid of aspartame, aspartic acid (200 mg), altered intake compared with placebo. Despite the large effect on food intake there were no treatment differences in pre- or postmeal ratings of motivation to eat. This suggests that aspartame may act to intensify the satiating effects of ingested food. Although high doses of phenylalanine reduce food intake, an individual action of phenylalanine cannot account for the potent anorexic effect of aspartame. In discussing alternative mechanisms it is noted that the amino acid sequence of aspartame (Asp-Phe) is the same as the C-terminal dipeptide of CCK. A direct action of aspartame at CCK receptors appears to be unlikely; however, aspartame might act as CCK releaser. Further studies are required to elucidate the mechanism of aspartame's anorexic action and perhaps to evaluate its therapeutic potential as an antiobesity agent.

Adult↗
PubMed1983

Monoclonal antibodies to the synthetic adjuvant muramyl dipeptide: characterization of the specificity.

Monoclonal antibodies to MDP were prepared by hybridization of NSO myeloma cells with spleen cells of BALB/c mice immunized with MDP conjugated to methyl-BSA. Hybridomas secreting anti-MDP antibodies were selected by the binding activity of their supernates to MDP-A--L using a radioimmunoassay. After cloning in soft agar, the specificities of monoclonal anti-MDP antibodies were assayed by an inhibition of ELISA with various derivatives of MDP. Fine structural analysis of specificity for one such clone (2-4) is reported. This antibody recognizes the N-acetyl-muramic acid (N-Ac-Mur) linked to the dipeptide but not N-Ac-Mur or/and dipeptide alone. The N-Ac group on muramic acid is an important antigenic determinant and the glycopeptide linkage seems to be crucial in presenting the sugar moiety. Conservative substitution of L-Ala (i.e. by L-Ser or L-Val) had no effect on the binding ability to the antibody whereas a radical change, i.e. replacement of L-Ala by L-Pro or N-methyl-L-Ala completely abolished the antigenicity of the molecule. There was no clear correlation between biological activities of various derivatives of MDP and their ability to react with this antibody. Some possible hypotheses explaining this lack of correlation are presented.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Serotonergic aspects of the response of human platelets to immune-adjuvant muramyl dipeptide.

The human platelet serotonergic responses of aggregation and uptake were shown to be modulated by muramyl peptides. Muramyl dipeptide inhibited serotonin uptake in a temperature dependent and stereospecific manner. It also blocked the binding to platelets of [3H]imipramine, a well-known inhibitor of serotonin uptake. Muramyl dipeptide decreased serotonin2 (5-HT2) mediated platelet aggregation, and blocked the binding of a 5-HT2-specific ligand: lysergic acid diethylamide. Since muramyl peptides are released upon degradation of bacteria, the findings offer a possible mechanism for neuro-immune modulation by emphasizing the interaction between 5-HT (a neurotransmitter) and muramyl peptides (immuno-adjuvants).

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Muscle buffering capacity and dipeptide content in the thoroughbred horse, greyhound dog and man.

1. Muscle buffering capacity (beta m) and dipeptide content were measured in locomotory muscles of the Thoroughbred horse, Greyhound dog and Man. 2. Beta m and carnosine contents were highest in the horse. Anserine was only found in dog muscle. 3. The higher beta m in horse and dog muscle, compared with man, appears to be predominantly due to higher muscle contents of histidine containing dipeptides in these species.

Animals↗
PubMed1990

Serotonin binding sites. II. Muramyl dipeptide binds to serotonin binding sites on myelin basic protein, LHRH, and MSH-ACTH 4-10.

Previously, we reported the existence of structurally similar serotonin binding sites on myelin basic protein, LHRH, and MSH-ACTH 4-10. We now report that the adjuvant peptide, muramyl dipeptide (N-acetyl-muramyl-L-Ala-D-isoGln) also binds to these sites. This observation may help to explain previous observations of serotonin-like activity by muramyl peptides, including the promotion of slow-wave sleep and fever induction. The observation may also provide an important link between the immune system and the nervous system that may explain the role of muramyl dipeptide adjuvants in causing autoimmune diseases to serotonin-regulated proteins and their receptors, as well as the alterations in serotonin levels that are often observed in autoimmune diseases. The observation provides concrete evidence for a dual-antigen hypothesis for the induction of autoimmune diseases by an adjuvant-peptide complex. Application of such a mechanism for induction of autoimmunity may be of importance in understanding a number of postinfectious and postvaccinal neuropathies, and suggests a possible etiology for autism, in which many patients have high blood serotonin levels, autoimmune reactions to myelin basic protein, and antibodies to serotonin binding sites. Finally, the observation suggests that glycopeptides may act as neurotransmitters.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Evaluation of the dipeptide and oligopeptide permeases of Candida albicans as uptake routes for synthetic anticandidal agents.

In order to obtain information essential for the design of synthetic anticandidal drugs that can exploit peptide permeases to gain access to intracellular targets, the substrate specificities of the dipeptide permease (Dpp) and oligopeptide permease (Opp) of Candida albicans have been studied. The permeases show strict stereospecificity, a preference for large, hydrophobic and N-terminal Ala residues, and marked discrimination against basic and acidic side chain residues. Comparison of results from several transport assays indicated that measuring loss of peptide substrate from the medium using fluorescence labelling procedures gave reliable transport rates and kinetic parameters, whereas in contrast, measuring accumulation of radioactivity from labelled substrates gave erroneous results arising from substrate metabolism and exodus. Intact accumulation of peptidase-resistant substrate against a concentration gradient was demonstrated. From amongst a variety of protein reagents tested, selective inhibition of dipeptide transport and presumed labelling of essential carboxyl group(s) in Dpp proteins was demonstrated using Woodward's reagent K.

Antifungal Agents↗
PubMed2006

Apoptosis and functional changes of dipeptide transporter (PepT1) in the rat small intestine after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) can induce significant alterations of intestinal mucosal structure and barrier function. However, it has not been investigated whether, and to what degree, apoptosis and alterations of absorptive function in the intestinal mucosal epithelium occur after TBI. MATERIAL AND METHODS: Male Wistar rats were randomly divided into seven groups (five rats each group) including normal group, control group with sham operation, and TBI groups at hours 3, 12, 24, and 72, and on day 7. Parietal brain contusion was adopted using weight-dropping method. Intestinal mucosal structure was examined using histomorphmetric study and electron microscopy, and apoptosis was detected by TUNEL method. An everted sleeve of intestine was securely incubated in Kreb's solution with radioactive dipeptide ((3)H-Gly-Sar, 10 microCi/mL) to measure the uptake and transport of PepT1 of small intestinal epithelial cells. RESULTS: The villous height, crypt depth and surface area were significantly decreased at 24 h after TBI, and further declined to the degree of mucosal atrophy on day 7 after TBI. Apoptotic changes of condensed nuclei in epithelial cells and fractured, distorted, and sparse microvilli were found by electron microscopy. The number of apoptotic cells in the mucosal epithelium was significantly increased since 3 h after TBI, peaked at 72 h post-injury, then declined at 7 days, but was still higher than that of control. There was a highly negative relation between the apoptotic index and the villous height, the crypt depth, and villous surface area. Compared with that of normal and control rats, the transport and uptake of dipeptide was significantly increased at 3 h post-injury (P < 0.01), peaked at 12 h and declined a bit at 24 h post-injury, and returned to the level of normal and control rats at 72 h and 7 days. CONCLUSIONS: It is highly suggested that intestinal mucosa apoptosis plays an important role in the pathogenesis of acute gut damage after TBI. Intestinal PepT1 expression could be up-regulated after traumatic brain injury, and maintained the normal level under the condition of serious intestinal damage. Up-regulation of PepT1 may adaptively improve absorption of di- and tripeptides, independent of changes in the mucosal surface area.

Adaptation, Physiological↗
PubMed2002

Dipeptidyl peptidase I: importance of progranzyme activation sequences, other dipeptide sequences, and the N-terminal amino group of synthetic substrates for enzyme activity.

The broadly reactive cysteine protease dipeptidyl peptidase I (DPPI, cathepsin C) is thought to activate all progranzymes (zymogens of lymphocyte serine proteases) to form mature granzymes. We synthesized dipeptide 7-amino-4-methylcoumarin (AMC) substrates containing progranzyme activation sequences and showed that they were efficiently hydrolyzed by DPPI. However, DPPI will not hydrolyze Ile-Ile-AMC, the N-terminal dipeptide sequence found in mature granzymes. Introduction of the nonphysiological homophenylalanine (Hph) residue at P1 resulted in the best substrate Ala-Hph-AMC for DPPI (k(cat)/K(m)=9,000,000M(-1)s(-1)). The charged N-terminal amino group of the substrate was essential and replacement of the NH(2) group with OH or NH(CH(3)) in Gly-Phe-AMC reduced the k(cat)/K(m) value by two to three orders of magnitude. A hydrazide azaglycine analog, NH(2)NHCO-Phe-AMC, was not hydrolyzed at pH 5.5, but underwent slow hydrolysis at lower pHs where the amino group is partially protonated. DPPI also failed to hydrolyze NH(2)COCH(2)-Phe-AMC, where the NH(2) group is unprotonated. The results reported in this paper should be useful in the design of better DPPI inhibitors to block granzyme maturation and granzyme-dependent apoptosis.

Catalytic Domain↗
PubMed2003

Molecular-level thermodynamic switch controls chemical equilibrium in sequence-specific hydrophobic interaction of 35 dipeptide pairs.

Applying the Planck-Benzinger methodology, the sequence-specific hydrophobic interactions of 35 dipeptide pairs were examined over a temperature range of 273-333 K, based on data reported by Nemethy and Scheraga in 1962. The hydrophobic interaction in these sequence-specific dipeptide pairs is highly similar in its thermodynamic behavior to that of other biological systems. The results imply that the negative Gibbs free energy change minimum at a well-defined stable temperature, , where the bound unavailable energy, TdeltaS(o) = 0, has its origin in the sequence-specific hydrophobic interactions, are highly dependent on details of molecular structure. Each case confirms the existence of a thermodynamic molecular switch wherein a change of sign in deltaCp(o)(T)(reaction) (change in specific heat capacity of reaction at constant pressure) leads to true negative minimum in the Gibbs free energy change of reaction, deltaG(o)(T)(reaction), and hence a maximum in the related equilibrium constant, K(eq). Indeed, all interacting biological systems examined to date by Chun using the Planck-Benzinger methodology have shown such a thermodynamic switch at the molecular level, suggesting its existence may be universal.

Amino Acid Sequence↗
PubMed2000

Solid-phase synthesis of muramyl dipeptide (MDP) derivatives using a multipin method.

Solid-phase synthetic method of muramyl dipeptide derivatives is reported. A diverse library of muramyl dipeptides could be potentially synthesized by acylation, reductive alkylation, sulfonamide formation, urea formation, N-alkylation, amine addition, or component Ugi reactions based on this method for drug screening.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMedDate not supplied

Activation of mouse macrophages by muramyl dipeptide coupled with an anti-macrophage monoclonal antibody.

A rat IgG2a monoclonal antibody (mAb3A33) directed against the mouse Mac-1 antigen was conjugated with muramyl dipeptide (MDP) by using an intermediate polymer; under such conditions 75 MDP molecules were bound to one antibody molecule. A poly(L-lysine) polymer substituted with muramyl dipeptide and 3-(2-pyridyldithio)propionyl residues were prepared, the remaining lysine epsilon-amino groups were acylated with D-gluconolactone, leading to a neutral polymer; then a few polymer conjugates were coupled to mAb3A33 via a disulfide bridge. The binding capacity of the monoclonal antibody was preserved after conjugation with MDP-polymer molecules. Mouse peritoneal macrophages, incubated for 24 h with MDP-mAb3A33 conjugate became cytostatic against P815 mastocytoma cells, whereas unconjugated mAb3A33 and MDP-bound to a nonspecific rat IgG2a were ineffective. An enhancement of the cytostatic activity induced by MDP-mAb3A33 conjugate was obtained in the presence of gamma-IFN. These results show that several tens of MDP molecules can be linked to a macrophage-specific monoclonal antibody by using a neutral intermediate polymer without impairing the binding antibody capacity and that this type of MDP conjugate can efficiently activate macrophages and therefore could be the basis of the development of new antitumor therapy.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

N-(2-chloroethyl)-N-nitrosoureas covalently bound to nonionic and monocationic lexitropsin dipeptides. Synthesis, DNA affinity binding characteristics, and reactions with 32P-end-labeled DNA.

The synthesis and characterization of a series of compounds that contain an N-alkyl-N-nitrosourea functionality linked to DNA minor groove binding bi- and tripeptides (lexitropsins or information-reading peptides) based on methylpyrrole-2-carboxamide subunits are described. The lexitropsins (lex) synthesized have either a 3-(dimethylamino)propyl or propyl substituent on the carboxyl terminus. The preferred DNA affinity binding sequences of these compounds were footprinted in 32P-end-labeled restriction fragments with methidiumpropyl-EDTA.Fe(II), and in common with other structural analogues, e.g., distamycin and netropsin, these nitrosoureas recognize A-T-rich runs. The affinity binding of the compound with the dimethylamino terminus, which is ionized at near-neutral pH, appeared stronger than that observed for the neutral dipeptide. The sequence specificity for DNA alkylation by (2-chloroethyl)nitrosourea-lex dipeptides (Cl-ENU-lex), with neutral and charged carboxyl termini, using 32P-end-labeled restriction fragments, was determined by the conversion of the adducted sites into single-strand breaks by sequential heating at neutral pH and exposure to base. The DNA cleavage sites were visualized by polyacrylamide gel electrophoresis and autoradiography. The alkylation of DNA by Cl-ENU-lex was compared to that by N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea (CCNU), which has no DNA affinity binding properties. While all the Cl-ENU compounds generate DNA breaks as a consequence of the formation of N7-alkyl-guanine, the Cl-ENU-lex compounds induced, in a time- and dose-dependent fashion, intense DNA cleavage bands at adenine, cytosine, and thymine residues associated with affinity binding sites. These non-G cleavages induced by Cl-ENU-lex were inhibited by the coaddition of distamycin at concentrations that did not affect G alkylation break sites. CCNU, even at much higher concentrations, does not generate any similar detectable lesions at non-G sites. Therefore, linking the Cl-ENU moiety to minor groove binders is a viable strategy to qualitatively and quantitatively control the delivery and release of the ultimate DNA alkylating agent in a sequence-dependent fashion.

Alkylation↗
PubMed2004

Calreticulin is a binding protein for muramyl dipeptide and peptidoglycan in RK13 cells.

Calreticulin (CRT) was isolated and identified as a protein in rabbit kidney RK(13) cells that binds the apoptogenic bacterial cell wall (BCW) components, muramyl dipeptide (MDP) and peptidoglycan (PG). Mannan-agarose purified RK(13) cell CRT (rCRT) selectively bound sepharose-immobilized L,D-MDP and PG, but not L,L-MDP or D,D-MDP. Purified rCRT and bovine CRT (bCRT) also bound free PG and L,D-MDP demonstrated in bioassays of RK(13) cell apoptosis. The results suggest that, in RK(13) cells, (a) CRT is a specific binding protein for both L,D-MDP and PG and (b) CRT binding L,D-MDP or PG is dependent on the stereoisomeric configuration of the dipeptide (L-alanyl-D-isoglutamine) moiety. In addition, the results also suggest that, in RK(13) cells, the binding of L,D-MDP, L,L-MDP, D,D-MDP, or PG to CRT correlates with their capacities of inducing apoptosis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Structure--sweetness relationship of L-aspartyl dipeptide analogues. A receptor site topology.

The relationship between structure and the sweet potency of L-aspartyl dipeptide analogues was investigated by physicochemical parameters and regression analysis. The dipeptide analogues reported were divided into the following four classes: L-aspartic acid amides, L-aspartylaminoethyl esters, L-aspartylaminopropionates, and L-aspartyl-aminoacetates. The analysis carried out for each class indicated that the electron-withdrawing effect of the substituents directed to the peptide bond and the steric dimensions of the molecules are important in eliciting the sweet taste. The values of coefficients of the electronic sigma terms in the correlations for L-aspartic acid amides, L-aspartylaminoethyl esters, and L-aspartylaminopropionates were approximately 0.7, indicating a common basic site on the receptor surface. The value for L-aspartylaminoacetates was approximately 1.5, and this value suggests, together with the factor of the participation of steric parameters, a closer or geometrically more proper fit to the receptor, explaining the generally higher potency of this class compared to the other three. The receptor model drawn based on these quantitative analyses appears to be consistent with other classes of sweeteners of apparently unrelated structures.

Aspartic Acid↗