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At least 883 records · Page 49Linked to original sources
PubMed1990

Influence of amino acid side-chain modification on the uptake system for beta-lactam antibiotics and dipeptides from rabbit small intestine.

The influence of chemical modification of functional amino acid side-chains in proteins on the H(+)-dependent uptake system for orally active alpha-amino-beta-lactam antibiotics and small peptides was investigated in brush-border membrane vesicles from rabbit small intestine. Neither a modification of cysteine residues by HgCl2, NEM, DTNB or PHMB and of vicinal thiol groups by PAO nor a modification of disulfide bonds by DTT showed any inhibition on the uptake of cephalexin, a substrate of the intestinal peptide transporter. In contrast, the Na(+)-dependent uptake systems for D-glucose and L-alanine were greatly inhibited by the thiol-modifying agents. With reagents for hydroxyl groups, carboxyl groups or arginine the transport activity for beta-lactam antibiotics also remained unchanged, whereas the uptake of D-glucose and L-alanine was inhibited by the carboxyl specific reagent DCCD. A modification of tyrosine residues with N-acetylimidazole inhibited the peptide transport system and did not affect the uptake systems for D-glucose and L-alanine. The involvement of histidine residues in the transport of orally active alpha-amino-beta-lactam antibiotics and small peptides (Kramer, W. et al. (1988) Biochim. Biophys. Acta 943, 288-296) was further substantiated by photoaffinity labeling studies using a new photoreactive derivative of the orally active cephalosporin cephalexin, 3-[phenyl-4-3H]azidocephalexin, which still carries the alpha-amino group being essential for oral activity. 3-Azidocephalexin competitively inhibited the uptake of cephalexin into brush-border membrane vesicles. The photoaffinity labeling of the 127 kDa binding protein for beta-lactam antibiotics with this photoprobe was decreased by the presence of cephalexin, benzylpenicillin or dipeptides. A modification of histidine residues in brush-border membrane vesicles with DEP led to a decreased labeling of the putative peptide transporter of Mr 127,000 compared to controls. This indicates a decrease in the affinity of the peptide transporter for alpha-amino-beta-lactam antibiotics by modification of histidine residues. The data presented demonstrate an involvement of tyrosine and histidine residues in the transport of orally active alpha-amino-beta-lactam antibiotics across the enterocyte brush-border membrane.

Affinity Labels↗
PubMed1976

An experimental and theoretical investigation of the core level spectra of a series of amino acids, dipeptides and polypeptides.

A series of simple amino acids, dipeptides and polypeptides have been studied experimentally by electron spectroscopy for chemical analysis and the results theoretically quantified using the charge potential model and semi-empirically computed charge distributions, and non-empirical calculations of absolute and relative binding energies for model systems. Core binding energies are shown to be characteristic of given structural features and the experimental data taken in conjunction with the model theoretical calculations indicate a zwitterionic structure with extensive intermolecular hydrogen bonding for simple amino acids in the solid state.

Amino Acids↗
PubMed1985

Dipeptide glycols: a new class of renin inhibitors.

The discovery of a new class of novel renin inhibitors consisting of protected dipeptide amides derived from aminoglycols (Formula I) prompted a study of structure-activity in vitro and efficacy in vivo. Thus, Boc-L-Phe-N-[(1S,2R)-1-benzyl-(2,3-dihydroxy)propyl]-L-leucinamide (1) and the corresponding histidinamide (2) inhibit human renin in vitro (IC50: 8.7 X 10-6 M and 2.6 X 10-6 M, respectively). Compound 1 has a slight inhibitory effect on pepsin and compound 2 does not inhibit pepsin at all (at 10-4M); these compounds are inactive against rat renin. Compound 1 is efficacious in lowering plasma renin activity in the Rhesus monkey (i.v.). Results indicate that this new class of low molecular weight inhibitors is specific for human renin and thus constitutes a new source of drug candidates.

Animals↗
PubMed1986

Influence of dipeptides on the interaction of immunoglobulins with bacterial Fc receptors.

Binding of radiolabeled human IgG to bacteria expressing type I, type II, or type III Fc receptors in the presence of glycyl-glycine, glycyl-tyrosine, glycyl-histidine, glycyl-leucine, or glycyl-phenylalanine was studied. No inhibition of labeled human IgG binding to type I or type III Fc receptor positive bacteria was observed by any of the dipeptides. Inhibition of binding of labeled human IgG1, IgG2, and IgG4, but not IgG3, indicated the presence of two distinct Fc receptors associated with the type II Fc receptor-positive group A streptococcal strain.

Dipeptides↗
PubMed1987

Enhanced potency dipeptide glycol renin inhibitors: studies in vitro and in the conscious rhesus.

We prepared a series of novel dipeptide amides of the formula Boc-Phe-Leu-X, where X is a 3-amino-3-alkyl-1,2-propanediol with lower alkyl substitutions at C-1, in order to probe accessory binding sites in the enzyme renin. This approach was successful in generating potent inhibitors of human and hog renin in vitro. Moreover, these inhibitors were able to effect in vivo reduction of plasma renin activity (PRA) in the conscious salt-depleted rhesus monkey (i.v. route); this effect was related to the size of the C-1 alkyl group.

Animals↗
PubMed1990

Specific inhibitory conformation of dipeptides for chymotrypsin.

Based on the analyzed conformation of a chymotrypsin inhibitor H-delta Phe-Phe-OMe, we have designed a series of diastereomeric phenylalanylphenylalanine methyl esters and derivatives as possible inhibitors. Among the peptides synthesized, H-D-Phe-L-Phe-OMe was found to be very resistant to chymotrypsin in spite of its L-Phe-OMe structure at the C-terminus. It inhibited the enzyme fairly strongly and competitively with Ki = 9.0 x 10(-5) M in the assay using Ac-Tyr-OEt as a substrate. The measurements of the NOEs in high-resolution 1H-NMR analyses indicated the presence of the hydrophobic core built by the intramolecular interaction between the D-Phe-phenyl and ester-methyl groups. It was suggested that this core interacts with the chymotrypsin S2 site (Trp215) and Phe2 with the S1 site. The backbone structure of this dipeptide was assumed to be in an inhibitory conformation that fits the active center of the enzyme.

Amino Acid Sequence↗
PubMed1992

Dipeptide inhibitors of ubiquitin-mediated protein turnover prevent growth factor-induced neurite outgrowth in rat pheochromocytoma PC12 cells.

Dipeptide inhibitors of the ubiquitin-dependent proteolysis pathway governed by N-terminal recognition (N-end rule) in reticulocyte lysates significantly suppress NGF- and bFGF-induced neurite outgrowth in rat pheochromocytoma PC12 cells, but do not cause retraction of already formed neurites. Peptides which do not inhibit proteolysis are also without effect on PC12 cell differentiation. Suppression of neurite outgrowth is readily reversible upon removal of the inhibitors. These data demonstrate a requirement for specific protein turnover in the process of neuron-like differentiation in PC12 cells and provide the first demonstration of a physiological role for the N-end rule.

Animals↗
PubMed1980

Regional distribution of a novel analgesic dipeptide kyotorphin (Tyr-Arg) in the rat brain and spinal cord.

Using high performance liquid chromatography, we measured kyotorphin content in discrete regions of the rat brain and spinal cord in an attempt to clarify its physiological significance. Higher concentrations of the dipeptide were found in the midbrain, pons plus medulla oblongata and dorsal cord, which are the most sensitive sites for the microinjection of morphine and/or electrical stimulation-induced analgesia. Kyotorphin may play a physiological role in pain control in the central nervous system.

Animals↗
PubMed1986

Human renin inhibiting dipeptide.

KRI-1177, a dipeptide containing nor-statine inhibited renin activity in human and Japanese monkey plasma to a markedly greater extent than that in dog, rabbit and rat plasma. The systemic blood pressure of anesthetized monkeys was lowered by intravenous injections of this compound which also reduced plasma renin activity and concentration of angiotensins. KRI-1177 appears to selectively inhibit primate renin activity, thereby producing hypotension.

Animals↗
PubMed1994

Effect of free glutamine and alanyl-glutamine dipeptide on mucosal proliferation of the human ileum and colon.

BACKGROUND/AIMS: Glutamine (Gln) is considered a trophic factor for small intestinal epithelia, which is important during severe illness. Its use in parenteral nutrition is precluded by its instability, a problem that may be overcome by use of the stable dipeptide L-alanyl-L-glutamine (Ala-Gln). The hypothesis was tested that Gln or Ala-Gln may stimulate cell proliferation not only in the ileum but also in the proximal and distal colon and, thus, may contribute to the gut barrier function. METHODS: Biopsy samples from the normal human ileum, proximal colon, and rectosigmoid were incubated for 4 hours with Gln (2 mmol/L), Ala-Gln (2 mmol/L), and saline (control). Cells in S phase were labeled with bromodeoxyuridine. In longitudinal crypt sections labeled and quiescent cells were counted. RESULTS: Gln as well as Ala-Gln stimulated crypt cell proliferation in the ileum, proximal colon, and rectosigmoid colon. In ileal specimens, labeling was greater in the entire crypt, whereas in both colonic regions, the trophic effect was confined to the basal crypt compartments. CONCLUSIONS: Gln and Ala-Gln have trophic effects not only in the ileum, but also in the proximal and distal colon. This could be important during parenteral nutrition when mucosal atrophy may weaken the gut barrier.

Adult↗
PubMed1990

Effects of mobile phase composition on the reversed-phase separation of dipeptides and tripeptides with cyclodextrin-bonded-phase columns.

The effects of mobile phase composition on the reversed-phase separation of several dipeptides and tripeptides with a gamma-cyclodextrin-bonded-phase column have been studied. The addition of organic modifier (i.e. methanol) into the aqueous buffer (pH 4.65) mobile phase causes a minimum capacity factor value to be observed for each peptide. This is interpreted to result from two retention mechanisms involved in the separation. The adsorption process causes the retention time to decrease as the water content in the mobile phase is increased. The inclusion process acts in the opposite fashion. The presence of Cu(II) salt in the mobile phase allows further modifications of separation selectivity. This is because the peptide conformation changes upon Cu(II) complexation which in turn alter the hydrophobicity and/or inclusion stability of the peptide. The effects of mobile phase pH (3.6-5.6) and ionic strength (0.001-0.06) were not significant in the present application. Studies with a beta-cyclodextrin column show similar results.

1-Propanol↗
PubMed1996

Kinetic study on the cis-trans isomerization of peptidyl-proline dipeptides.

The equilibrium and kinetic parameters of cis-trans interconversion of dipeptides containing peptidyl-proline moiety were investigated using the in-column incubation method with both CZE and HPLC and the ad hoc dissolution method. The use of the latter was possible because the conformational make-up of the solid peptides, and consequently of their ad hoc solution, was sufficiently different from that of the solution at equilibrium. This method with 1H-NMR and CZE analyses yielded very similar results for the cis-trans isomerization of Phe Pro in aqueous sodium borate, pH 8.4, at 10 degrees C with an average value of 0.34 and 6.6 x 10(-5) s-1 for the equilibrium and rate constant, respectively. The in-column incubation method is performed by CZE or HPLC so that the conformers are separated in the first half of the column and then incubated in column where they interconvert and reach equilibrium. Subsequent separation in the second half of the column yielded four peaks. Thus by measuring the conformer composition as a function of the reaction time, the rate constant can be evaluated. The forward rate constant of 1.42 x 10(-4) s-1 determined by the CZE in-column incubation method for Phe-Pro isomerization at 10 degrees C was twice of the value obtained by the ad hoc dissolution method. It is believed that the inner wall of fused-silica capillaries has a catalytic effect on the isomerization. Computer simulation was also employed to gain further insight on the catalytic activity of the capillary inner wall on such isomerization. Whereas the experimental and simulation profiles of Phe-Pro in aqueous borate buffer, pH 8.4, with a 37 cm long capillary were in excellent agreement, a four times faster interconversion rate had to be used to match the experimental profile obtained with a 57 cm long capillary under otherwise identical conditions. The catalytic effect of the octadecyl silica stationary phase on the isomerization was confirmed by the in-column incubation method with HPLC. The overall rate of the cis-trans isomerization of Phe-Pro, which entails the reaction both on the stationary phase and in the mobility phase, was about six times faster at 0 degree C than the rate measured by NMR in free solution using the mobile phase containing 65% (v/v) sodium phosphate, pH 6.5, and 35% (v/v) methanol. The results presented here serve as a caveat that the effect of the wall in CZE or the stationary phase in HPLC on the reaction cannot be ignored.

Chromatography, High Pressure Liquid↗
PubMed1994

Importance of liver and kidney for the utilization of glutamine-containing dipeptides in man.

The impact of hepatic and renal failure on the metabolism of L-alanyl-L-glutamine (Ala-Gln) and glycyl-L-glutamine (Gly-Gln) was investigated in 11 healthy volunteers, five patients with liver cirrhosis, and six patients with chronic renal failure. The clearance (mL.kg-1.min-1) of Ala-Gln was significantly higher than that of Gly-Gln in all three groups. Renal failure significantly reduced clearances of both Ala-Gln and Gly-Gln (13.27 +/- 0.71 and 3.06 +/- 0.28) when compared with control values (21.68 +/- 1.21 and 7.08 +/- 0.38). Liver failure had no significant influence on the clearances of Ala-Gln and Gly-Gln (22.62 +/- 2.89 and 6.20 +/- 0.88). Liver failure delayed and renal failure almost abolished the increases in plasma concentrations of free amino acid residues after peptide injection. It is concluded that other organs can substitute for the peptide-clearing function of the liver, but not of the kidney. Kidney is the most important organ for the clearance of dipeptides and the release of amino acid residues into circulation. Our data show that clearance rates of both Ala-Gln and Gly-Gln are sufficient to avoid accumulation of either peptide if infused in the presently recommended doses. Both Ala-Gln and Gly-Gln could therefore be used as sources for glutamine in parenteral nutrition even in patients with chronic renal failure.

Adult↗
PubMed1990

Papain-catalysed synthesis of dipeptides: a novel approach using free amino acids as nucleophiles.

For the first time, papain-catalysed synthesis of peptide bonds was successfully carried out using free amino acids as nucleophiles. In kinetically controlled experiments employing pH-Stat-mode, the ester substrates Z-Ala-OMe and Z-Gly-OMe were coupled with alanine, glutamine, and Cys(Acm)-OH, respectively. Under optimized reaction conditions (pH 9.2, high ratio nucleophile/carboxyl component, 10 mumol substrate mg-1 papain), the peptide yields ranged from 17% to 79%, depending on the structure of the amino and/or carboxyl component. The peptides formed were not hydrolysed under the chosen reaction conditions. With Z-Gly-OMe as the ester substrate, formation of the dipeptide was both rapid and high yielding. Papain-catalysed formation of peptide bonds applying free amino acids as nucleophiles might serve as an economic and easily manageable approach for the synthesis of short-chain peptides to be used in clinical nutrition.

Amino Acid Sequence↗
PubMed1993

Copper(II) complexes of dipeptides containing aspartyl, glutamyl, and histidyl residues in the side chain.

Copper(II) complexes of various dipeptides containing carboxylate and imidazole-N3 donors (alpha- and gamma-GluVal, alpha- and beta-AspGly, beta-AspHis, gamma-GluHis, and homocarnosine) were studied by potentiometric and spectroscopic methods in solution. It was found that the presence of an alpha-carboxylate group in the N-terminal part of a peptide molecule significantly enhances the metal-binding ability of the ligands as a consequence of stable bis complex formation involving amino acid-like coordination. The interaction of copper(II) with beta-AspHis was characterized by the formation of an imidazole-bridged dimeric species, while the formation of bis complexes was detected in the case of gamma-GluHis. Binding of the imidazole N3 and deprotonated amide nitrogen was presumed in the copper(II)-homocarnosine system.

Aspartic Acid↗
PubMed1994

Adjuvant effect of liposomes and adamantylamide dipeptide on antigenicity of entrapped synthetic peptide derived from HIV-1 transmembrane region glycoprotein gp41.

The synthetic peptide antigen (Ag) (the primary structure Tyr-Leu-Lys-Asp-Gln-Gln-Leu-Leu-Gly-Ile-Trp-Gly-Cys-Ser-Gly-Lys-Leu-Ile- Cys-Thr derived from the envelope glycoprotein gp41 of the human immunodeficiency virus type 1 (HIV-1) and exerting specificity with all HIV-1-positive sera available in the Czech Republic (and also in a panel of 10,000 sera from WHO)) was conjugated with bovine serum albumin (BSA) and encapsulated into liposomes. Adjuvant activities of liposomes with various lipid compositions were compared with Freund's complete adjuvant (FCA) and with aluminium hydroxide (AL). The immune response to BSA-Ag liposomes with coentrapped adamantylamide dipeptide (AdDP) was comparable with that of FCA in terms of longevity and levels of specific antibodies in mouse sera.

Adjuvants, Immunologic↗
PubMed1985

Differential inhibition of DNA and RNA biosynthesis in HeLa S3 cells by tetaine, a dipeptide antibiotic.

A dipeptide antibiotic, tetaine, was found to diminish the rate of incorporation of 3H-labelled precursors into nucleic acids of intact and permeabilized HeLa S3 cells with concomitant negligible effect on protein synthesis. Comparison of the inhibitory effects of tetaine indicates that the antibiotic at 0.03-0.1 mM is a selective inhibitor of cellular DNA biosynthesis and, at higher concentration, of DNA and RNA biosynthesis. Tetaine is also an inhibitor of DNA and RNA polymerase reactions in a cell-free system, as determined using partially purified extracts from HeLa S3 cells that served as a source of the enzymes. The pretreatment experiments showed that tetaine inactivated the polymerases without affecting DNA template function. The tetaine effect on biosynthesis of nucleic acids in HeLa S3 cells can be attributed rather to the intact antibiotic than to the product of its enzymatic cleavage, anticapsin.

Alanine↗
PubMedDate not supplied

Antinociceptive effects in rodents of the dipeptide Lys-Trp (Nps) and related compounds.

Intracerebroventricular administration of the synthetic dipeptide derivative Lys-Trp (Nps) (LTN) elicits a potent and naloxone-sensitive antinociceptive effect in mice and in rats using heat and electrical current respectively as the noxious stimuli. LTN does not induce analgesia by directly acting on opioid receptors but the peptidase inhibiting activity of the new compound may account in part for the behavioral effect. LTN produces also a marked decrease in the met-enkephalin content of the periaqueductal gray suggesting a possible enkephalin releasing property. Structure-activity studies with different analogs of LTN indicate that replacement of Lys by other basic amino acids results also in compounds with a potent antinociceptive effect whereas replacement by neutral or acidic amino acids leads to a complete loss of activity.

Analgesia↗