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 73 records · Page 4Linked to original sources
PubMed1986

Kinetics and characteristics of absorption from an equimolar mixture of 12 glycyl-dipeptides in human jejunum.

We have investigated rates of dipeptide disappearance during jejunal perfusion with an equimolar mixture of 12 glycyl-dipeptides and compared amino acid absorption rates from this mixture with those from the corresponding free amino acid mixture in healthy volunteers. All dipeptides contained glycine in the N-terminal position, which was designed to favor peptide absorption rather than hydrolysis. At 2 mM concentration there was little difference in disappearance among dipeptides, but at 6 mM there was some selectivity: Gly-Phe and Gly-Met exhibited the fastest, and Gly-Arg and Gly-His the slowest rates of disappearance. However, between these ends of the spectrum there were only modest differences in disappearance among dipeptides (Gly-Ala, Gly-Thr, Gly-Leu, Gly-Ile, Gly-Val, Gly-Lys, Gly-Pro, Gly-Trp). The amino acid absorption rates were generally smaller but more selective from the free amino acid than from the dipeptide mixture. We conclude that (a) the C-terminal amino acid residue influences intestinal assimilation of glycyl-dipeptides and (b) the considerably greater absorption rate of amino acids from the dipeptide than from the amino acid mixture appears to be the result of uptake by a system that has a greater transport capacity than amino acid carrier systems, thus minimizing competition among its substrates.

Adult↗
PubMed1986

Influence of molecular structure on half-life and hydrolysis of dipeptides in plasma: importance of glycine as N-terminal amino acid residue.

To investigate the effect of molecular structure on plasma disappearance and metabolism of dipeptides, rats were injected intravenously with individual dipeptides, and at various intervals after injection, dipeptide and amino acid concentrations were measured in plasma, tissues, and urine. In addition, plasma hydrolase activity against individual dipeptides was investigated. The half-lives of Ala-Leu, Ala-Tyr, and Ala-Gln were shorter than those of dipeptides with glycine substituting for alanine. Furthermore, the increases in plasma concentrations of leucine, tyrosine, and glutamine and rates of dipeptide hydrolysis by plasma enzymes were far greater with alanyl than glycyl dipeptides. In fact, Ala-Leu behaved like a mixture of corresponding free amino acids in raising the plasma concentration of leucine while Gly-Leu did not. There was no significant difference in either plasma half-life or hydrolysis when Leu-Gly and Leu-Ala were used as substrates, but both had rapid rates of hydrolysis in plasma. In comparison to Gly-Leu, Phe-Leu and Arg-Leu had shorter half-lives and greater rates of hydrolysis in plasma. On the other hand, Asp-Leu had a slower rate of plasma hydrolysis than Gly-Leu, but its excretion in the urine was much greater than that of Gly-Leu. In contrast to Gly-Leu and Ala-Leu, Gly-Pro was detected intracellularly in liver, muscle, and particularly, kidney. In fact, the intracellular concentration of Gly-Pro in kidney was either equal to or greater than Gly-Pro concentration in plasma. Increases in intracellular amino acid concentration after injection of individual dipeptides were considerably greater in the kidney than in either liver or muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1985

Synthesis of polyetherurethanes containing L-serine dipeptide and their use as materials for biomedical films.

Prepolymers, which were produced by the polyaddition reaction of polytetramethylene glycol (PTMG) or polyethylene glycol (PEG) and 4,4'-diphenylmethane diisocyanate (MDI) or hexamethylene diisocyanate (HMDI), were chain-extended with a linear dipeptide of L-serine (Z-Ser-Ser-OMe) or a cyclic dipeptide of L-serine [c-(Ser)2] to yield novel polyetherurethanes containing dipeptide segments. The relationship between the surface morphology and the biomedical properties of the film of the novel polyetherurethanes was investigated. The surface of PU(PTMG,Z-Ser-Ser-OMe,MDI) film was smooth, but fibrous structures were developed in the bulk of the film with increasing molecular weight of the PTMG segment. The antithrombogenicity of the film containing the low molecular weight PTMG segment was better than that of the usual polyetherurethane film without the dipeptide segments. The partial hydrolysis of the ester groups involved in the dipeptide segment improved the antithrombogenicity. In the surface and the bulk of PU[PTMG,c-(Ser)2,MDI] film, spherulite structures were developed when the molecular weight of the PTMG segment was high, while single crystals with a length of 3-4 microns were produced when the molecular weight of the PTMG segment was low. The antithrombogenicity of the film containing the high molecular weight PTMG segment was better than that of the usual polyetherurethane film without the dipeptide segments. PU(PTMG/PEG,Z-Ser-Ser-OMe,MDI) film and PU[PTMG/PEG,c-(Ser)2,MDI] film were permeated by uraemic toxins. The permeation was accelerated with increasing water content of the film and decreasing molecular weight of the solute. The oxygen permeability of the film of the polyetherurethane containing the linear or cyclic dipeptide segments was greater than that of polyetherurethane film which does not contain the dipeptide segments.

Biocompatible Materials↗
PubMed2004

The membrane-associated lipoprotein-9 GmpC from Staphylococcus aureus binds the dipeptide GlyMet via side chain interactions.

Bacterial dipeptide ABC transporters function to import a wide range of dipeptide substrates. This ability to transport a wide variety of dipeptides is conferred by the cognate substrate binding protein (SBP) of these transporters. SBPs bind dipeptides with little regard for their amino acid content. Here, we report the 1.7 A resolution structure of lipoprotein-9 (SA0422) of Staphylococcus aureus in complex with the dipeptide glycylmethionine. Experimental characterization of the subcellular location of the protein confirmed that SA0422 is an acylated, peripheral membrane protein. This is the first structure determined for an SBP of a Gram-positive dipeptide ABC transporter. Usually, binding of dipeptides occurs in a binding pocket that is largely hydrated and able to accommodate the side chains of several different amino acid residues. Unlike any other known SBP, lipoprotein-9 binds the side chains of the glycylmethionine dipeptide through very specific interactions. Lipoprotein-9 shares significant structural and sequence homology with the MetQ family of methionine SBP. Sequence comparisons between MetQ-like proteins and lipoprotein-9 suggest that the residues forming the tight interactions with the methionine side chains of the ligand are highly conserved between lipoprotein-9 and MetQ homologues, while the residues involved in coordinating the glycine residue are not. Modeling of the Vibrio cholerae MetQ and lipoprotein-9 binding pockets can account for lipoprotein-9 substrate specificity toward glycylmethionine. For this reason, we have designated lipoprotein-9 GmpC, for glycylmethionine binding protein.

Amino Acid Sequence↗
PubMed2001

Chirality organization of ferrocenes bearing podand dipeptide chains: synthesis and structural characterization.

A variety of ferrocenes bearing podand dipeptide chains have been synthesized to form an ordered structure in both solid and solution states and have been investigated by 1H NMR, FT-IR, CD, and X-ray crystallographic analyses. Conformational enantiomerization through chirality organization was achieved by the intramolecular hydrogen bondings between the podand dipeptide chains. The single-crystal X-ray structure determination of the ferrocene 2 bearing the podand dipeptide chains (-D-Ala-D-Pro-OEt) revealed two C2-symmetric intramolecular hydrogen bondings between CO (Ala) and NH (another Ala) of each podand dipeptide chain to induce the chirality-organized structure. The molecular structures of the ferrocene 1 composed of the podand L-dipeptide chains (-L-Ala-L-Pro-OEt) and 2 are in a good mirror image relationship, indicating that they are conformational enantiomers. An opposite helically ordered molecular arrangement was formed in the crystal packing of 2 as compared with 1. The ferrocene 2 exhibited induced circular dichroism (CD), which appeared at the absorbance of the ferrocene moiety. The mirror image of the CD signals between 1 and 2 was observed, suggesting that the chirality-organized structure via intramolecular hydrogen bondings is present even in solution. The ferrocene 4 bearing the podand dipeptide chains (-Gly-L-Leu-OEt) also showed an ordered structure in the crystal based on two intramolecular hydrogen bondings between CO (Gly) and NH (another Gly) of each podand dipeptide chain, together with intermolecular hydrogen bondings between CO adjacent to the ferrocene unit and NH (neighboring Leu) to create the highly organized self-assembly. A different self-assembly was observed in the crystal of the ferrocene 5 composed of the podand dipeptide chains (-Gly-L-Phe-OEt), wherein each molecule is bonded to two neighboring molecules through two pairs of symmetrical intermolecular hydrogen bonds to form a 14-membered intermolecularly hydrogen-bonded ring. These ordered structures based on the intramolecular hydrogen bondings in the solution state are also confirmed by 1H NMR and FT-IR.

Circular Dichroism↗
PubMed1998

X-ray crystal structure of a dipeptide-chymotrypsin complex in an inhibitory interaction.

The dipeptide D-leucyl-L-phenylalanyl p-fluorobenzylamide (D-Leu-Phe-NH-BzlF) inhibits chymotrypsin strongly in a competitive manner with the Ki value of 0.61 microM [Shimohigashi, Y., Maeda, I., Nose, T., Ikesue, K., Sakamoto, H., Ogawa, T., Ide, Y., Kawahara, M., Nezu, T., Terada, Y., Kawano, K. & Ohno, M. (1996) J. Chem. Soc. Perkin Trans. 1, 2479-2485]. The structure/activity studies have suggested a unique inhibitory conformation, in which the C-terminal benzyl group fits the chymotrypsin S1 site and the hydrophobic core constructed by the side chains of D-Leu-Phe fits the S2 or S1' site. To verify this assumption, the molecular structure of the complex between the dipeptide and gamma-chymotrypsin has been determined crystallographically. Gamma-chymotrypsin itself was first crystallized and refined at 1.6-A resolution. The refined structure was virtually identical to the conformation reported and the electron density at the active site was interpreted as a pentapeptide Thr-Pro-Gly-Val-Tyr derived from autolysis of the enzyme (residues 224-228). The chymotrypsin-dipeptide complex was obtained by soaking the crystals of gamma-chymotrypsin in a solution saturated with the dipeptide inhibitor. The crystal structure of the complex has been refined at 1.8-A resolution to a crystallographic R-factor of 18.1%. The structure of gamma-chymotrypsin in the complex agreed fairly well with that of gamma-chymotrypsin per se with a rmsd of 0.13 A for all the C alpha carbons. Two inhibitor molecules were assigned in an asymmetric unit, i.e. one in the active site and the other at the interface of two symmetry-related enzyme molecules. In both sites dipeptides adopted very similar folded conformations, in which side chains of D-Leu-Phe are spatially proximal. In the active site where the binding of dipeptide was judged to be a direct cause of inhibition, C-terminal p-fluorobenzylamide group of the dipeptide, NH-BzlF, was found in the S1 hydrophobic pocket. At the bottom of this pocket, the p-fluorine atom hydrogen bonded with a water molecule, probably to enhance the inhibitory activity. The stereospecific interaction of R and S isomers of the dipeptide with C-terminal NH-C*H(CH3)-C6H5 was well explained by the space available for methyl replacement in the complex. The hydrophobic core constructed by side chains of D-Leu-Phe was found at the broad S2 site. Interestingly, a novel interaction was found between the inhibitor Phe residue and chymotrypsin His57, the phenyl of Phe and the imidazole of His being in a pi-pi stacking interaction at a distance 3.75 A.

Benzamides↗
PubMedDate not supplied

Novel dipeptide prodrugs of acyclovir for ocular herpes infections: Bioreversion, antiviral activity and transport across rabbit cornea.

PURPOSE: A series of dipeptide prodrugs of antiviral nucleoside acyclovir (ACV) were designed to target the oligopeptide transporter on the cornea with an aim of improving the ocular bioavailability and therapeutic activity of ACV. METHODS: Aqueous stability, ocular bioreversion kinetics in various tissues, in vitro antiviral activity, cell proliferation assay and corneal transport characteristics of the dipeptide prodrugs were studied. Results. ACV dipeptide prodrugs were found to be more stable at pH 5.6 in comparison to L-Val-ACV, an amino acid prodrug of ACV. The prodrugs exhibited higher solubility than ACV. Val-Val-ACV and Val-Tyr-ACV were found to have excellent antiviral activity against herpes simplex virus-1 (HSV-1). All the dipeptide prodrugs exhibited lower cytotoxicity as compared to currently approved anti-HSV agent, trifluorothymidine (TFT). Transport of [(3)H] Val-ACV was inhibited significantly in the presence of the dipeptide prodrugs of ACV. Corneal permeabilities of all the ACV dipeptide prodrugs were observed to be higher than ACV possibly due to recognition of the prodrugs by the oligopeptide transporter on the cornea. CONCLUSIONS: The dipeptide prodrugs were found to be more permeable than the parent drug, ACV. More permeable, less cytotoxic ACV dipeptide prodrugs exhibited excellent chemical stability and antiviral activity against herpes simplex virus thereby rendering these lead compounds promising drug candidates against herpes virus infections.

Acyclovir↗
PubMed1995

Dipeptide transport and hydrolysis in isolated loops of rat small intestine: effects of stereospecificity.

1. Isolated jejunal loops of rat small intestine were perfused by a single pass of bicarbonate Krebs-Ringer solution containing either D- or L-phenylalanine or one of eight dipeptides formed from D- or L-alanine plus D- or L-phenylalanine. 2. At 0.5 mM L-phenylalanyl-L-alanine increased serosal phenylalanine appearance to forty times the control rate giving a value similar to that found with 0.5 mM free L-phenylalanine. No serosal dipeptide could be detected. 3. Perfusions with the two mixed dipeptides with N-terminal D-amino acids (D-alanyl-L-phenylalanine and D-phenylalanyl-L-alanine) gave rise to the appearance of intact dipeptides in the serosal secretions although there were substantial differences in their rates of absorption and subsequent hydrolysis. 4. L-Alanyl-D-phenylalanine was absorbed from the lumen three to five times as fast as L-phenylalanyl-D-alanine. At 1 mM L-alanyl-D-phenylalanine transferred D-phenylalanine across the epithelial layer at more than seven times the rate found with the same concentration of the free D-amino acid. 5. Perfusions with D-alanyl-D-phenylalanine or D-phenylalanyl-D-alanine showed that these two dipeptides are poor substrates for both transport and hydrolysis by the rat small intestine. 6. Analysis of mucosal tissue extracts after perfusion with the two mixed dipeptides with N-terminal D-amino acids revealed that both dipeptides were accumulated within the mucosa and suggested that exit across the basolateral membrane was rate limiting for transepithelial dipeptide transport.

Alanine↗
PubMed1986

A concentrated mixture of amino acids and dipeptides for total parenteral nutrition.

Using a subhuman primate (baboon) we have investigated the utility of a 20% mixture of amino acids and dipeptides as the nitrogen source for total parental nutrition. The mixture, besides containing all 8 essential amino acids and a number of non-essential amino acids (glutamate, aspartate, arginine, histidine, serine, ornithine and alanine), contained 6 dipeptides (Gly-Ile, Gly-Leu, Gly-Val, Gly-Tyr, Gly-Gln, and Ala-Gln) and acetyl-cysteine. A week of total parenteral nutrition was preceded by one week of oral feeding. The caloric intake and composition during the two periods was identical except for the nitrogen source, which was intact protein during the oral period, and the mixture of amino acids and dipeptides during the parenteral period. There was no significant difference between gain in body weight or nitrogen balance during the two periods. There were selective increases in plasma and muscle concentrations of amino acids during the parenteral period, which appeared to reflect the amino acid enrichment of the nitrogen source. The efficient utilization of dipeptides was evidenced by their small concentrations in plasma and urine. The urinary excretion of dipeptides was about 1% of the amount infused. This efficiency of dipeptide utilization persisted even when the infusion rate of the amino acid and dipeptide mixture was increased by 7-fold. There was no alteration in liver, kidney, and immune function during the parenteral period. The data indicate the efficacy and safety of the mixture of amino acids and dipeptides as the nitrogen source for parenteral nutrition.

Amino Acids↗
PubMed2000

Predominant torsional forms adopted by dipeptide conformers in solution: parameters for molecular recognition.

The present paper describes the predominant conformational forms adopted by dipeptides in aqueous solution. More than 50 dipeptides were subjected to conformational analysis using SYBYL Random Search. The resultant collections of conformers for individual dipeptides, for small groups with related side chain residues and for large groups of about 50 dipeptides were visualized graphically and analysed using a novel three-dimensional pseudo-Ramachandran plot. The distribution of conformers, weighted according to the percentage of each in the total conformer pool, was found to be restricted to nine main combinations of backbone psi (psi) and phi (phi) torsion angles. The preferred psi values were in sectors A7 (+150 degrees to +/-180 degrees), A10 (+60 degrees to +90 degrees) and A4 (-60 degrees to -90 degrees), and these were combined with preferred phi values in sectors B12 (-150 degrees to +/-180 degrees), B9 (-60 degrees to -90 degrees) and B2 (+30 degrees to +60 degrees). These combinations of psi and phi values are distinct from those found in common secondary structures of proteins. These results show that although dipeptides can each adopt many conformations in solution, each possesses a profile of common conformers that is quantifiable. A similarly weighted distribution of dipeptide conformers according to distance between amino-terminal nitrogen and carboxyl-terminal carbon shows how the preferred combinations of backbone torsional angles result in particular N-C geometries for the conformers. This approach gives insight into the important conformational parameters of dipeptides that provide the basis for their molecular recognition as substrates by widely distributed peptide transporters. It offers a basis for the rational design of peptide-based bioactive compounds able to exploit these transporters for targeting and delivery.

Computer Simulation↗
PubMed1995

Mechanism of lysosome rupture by dipeptides.

Low concentrations of some neutral dipeptides, such as L-Ala-L-Ala, rapidly disrupt rat liver lysosomes. The phenomenon has been attributed to an osmotic imbalance generated by the production of amino acids in the lysosome by lysosomal dipeptidase activity. This hypothesis is challenged by testing several pairs of dipeptides available in both D- and L-forms and a range of dipeptides whose susceptibility to lysosomal dipeptidase activity is known. A good correlation was found between the lytic ability of dipeptides and their capacity to cross the lysosome membrane and be hydrolysed by lysosomal dipeptidase. The osmotic-imbalance hypothesis is critically evaluated in the light of the results and of recent information concerning the carrier-mediated transport of amino acids and dipeptides across the lysosome membrane. It is concluded that intralysosomal generation of amino acids remains the most plausible explanation of the lytic activity of dipeptides, and that the dipeptide porter(s) in the lysosome membrane must have higher Km than the amino acid porters.

Animals↗
PubMed2006

Effects of structural and "mixed" isomers of Glu-Trp dipeptide on normal hemopoietic stem cells.

We studied the effects of optical (dd-, ll-, dl-, and ld-dipeptides with alpha-bond, EW) structural isomers and cyclic (dd-, ll-, dl-, and ld-dipeptides with gamma-bond, iEW) analogs of Glu-Trp synthetic dipeptide on the population of normal hemopoietic stem cells. Dipeptides containing lGlu (lGlu-lTrp, lGlu-dTrp) injected to mice were inert towards committed bone marrow CFU-S; dGlu-containing dipeptides (dGlu-dTrp, dGlu-lTrp) inhibited the growth of CFU-S-8; and LiGlu-dTrp stimulated these cells. Inhibitory or stimulatory effects of optical and chemical isomers of Glu-Trp dipeptide are determined by optical orientation and nature of peptide bond of Glu residue. The effects of cyclic and mixed peptides towards colony formation are similar to those of the corresponding linear dipeptides.

Animals↗
PubMed1995

Optimization of a modified electrode for the sensitive and selective detection of alpha-dipeptides.

Sensitive and selective detection of dipeptides is important in neurochemistry. We have developed a flexible detection scheme for dipeptides based on a modified carbon electrode. The modification arises from the anodic treatment of the carbon electrode in alkaline solution. The flexibility of the detection scheme arises from the different conditions used in both the modification and the detection. It is shown that the modification step requires the presence of cupric ion, while the detection step does not. On the other hand, it is shown that the presence of copper in the detection eluent, as well as the pH of the environment, can be used in controlling the selectivity of the modified electrode. For example, the modified electrode is more selective for alpha-dipeptides over beta- and gamma-dipeptides as well as amino acids at pH 9.8, whereas it is selective for all dipeptides over amino acids at pH 8.0. Detection limits of dipeptides on the order of 10 nM were achieved at pH 8.0 by flow-injection analysis with a knotted Teflon tubing connecting the injector and the detector that gave a typical peak volume of about 0.50 ml at 1.0 ml/min. From surface analysis it is shown that the oxygenation of the glassy carbon electrode gives rise to the selectivity. The oxidation of dipeptides at the modified electrode is completely inhibited by 10 mM Mg2+ in the eluent.

Chromatography, Liquid↗
PubMed2004

The influence of dipeptide composition on protein thermostability.

In this work, the influence of dipeptide composition on protein thermostability was studied. After comparing the normalized dipeptide composition between mesophilic proteins and (hyper)thermophilic proteins, we concluded that when organism optimal growth temperature increased, for archaeal proteins, the compositions of VK, KI, YK, IK, KV, KY, and EV increased significantly and the compositions of DA, AD, TD, DD, DT, HD, DH, DR, and DG decreased significantly; and for bacterial proteins, the compositions of KE, EE, EK, YE, VK, KV, KK, LK, EI, EV, RK, EF, KY, VE, KI, KG, EY, FK, KF, FE, KR, VY, MK, WK, and WE increased significantly and the compositions of WQ, AA, QA, MQ, AW, QW, QQ, RQ, QH, HQ, AD, AQ, WL, QL, HA, and DA decreased significantly. So these characteristic dipeptides are correlative to protein thermostability. At the same time, the influence of single amino acid composition on protein thermostability was also studied for comparison. We found that the influence of single amino acid composition could be deduced from the influence of dipeptide composition. So we thought that the influence of dipeptide composition on protein thermostability is larger than the influence of amino acid composition. The characteristic dipeptides not only describe the dipeptides that influence protein thermostability significantly but also show the relationship among significant single amino acids that influence protein thermostability.

Amino Acid Sequence↗
PubMed1996

Mechanistic implication of crystal structures of the cyclophilin-dipeptide complexes.

The structures of cyclophilin A complexed with dipeptides of Ser-Pro, His-Pro, and Gly-Pro have been determined and refined at high resolution. Comparison of these structures revealed that the dipeptide complexes have the same molecular conformation and the same binding of the dipeptides. The side chains of the N-terminal amino acid of the above dipeptides do not strongly interact with cyclophilin, implying their minor contribution to the cis-trans isomerization and thus accounting for the broad catalytic specificity of the enzyme. The binding of the dipeptides is similar to that of the common substrate succinyl-Ala-Ala-Pro-Phe-p-nitroanilide in terms of the N-terminal hydrogen bonding and the hydrophobic interaction of the proline side chain. However, substantial difference between these structures are observed in (1) hydrogen bonding between the carboxyl terminus of the peptides and Arg55 and between Arg55 and Gln63, (2) the side chain conformation of Arg55, and (3) water binding at the active site. These differences imply either that dipeptides are not substrates but competitive inhibitors of peptidyl-prolyl cis-trans isomerases or that dipeptides are subject to different catalytic mechanisms from tetrapeptides.

Amino Acid Isomerases↗
PubMed1997

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.

Animals↗
PubMed1998

The biological activity of selected cyclic dipeptides.

Cyclic dipeptides are widely used as models for larger peptides because of their simplicity and limited conformational freedom. Some cyclic dipeptides have been shown to be antiviral, antibiotic and anti-tumour. The aim of this study was to determine the biological activity of four cyclic dipeptides synthesized in this laboratory: cyclo(L-phenylalanyl-L-prolyl), cyclo(L-tyrosyl-L-prolyl), cyclo(L-tryptophanyl-L-prolyl) and cyclo(L-tryptophanyl-L-tryptophanyl). The enhancement or inhibition of calcium channels in ventricular myocytes from rats and delayed-rectifier potassium channels in ventricular myocytes from guinea-pigs were determined by use of the whole-cell patch-clamp technique. The induction of differentiation in HT-29 cells was assessed by assaying for an increase in the expression of alkaline phosphatase. Antibiotic properties against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilus and Streptococcus sp. were determined by use of the Kirby-Bauer disc-diffusion assay. Results from these assays indicate that the cyclic dipeptides have biological activity in both prokaryotes and eukaryotes. Three of the dipeptides block cation channels in ventricular myocytes and all increase the expression of alkaline phosphatase. All the dipeptides have concentration-dependent antibacterial properties. These results suggest that with increased solubility the cyclic dipeptides might have potential as muscle relaxants, anti-tumour compounds and antibiotics.

Anti-Bacterial Agents↗
PubMed1993

Dipeptide transporters in apical and basolateral membranes of the human intestinal cell line Caco-2.

The localization and transport characteristics of dipeptide transporters of the intestinal epithelial cell line Caco-2 were examined by measuring the intracellular accumulation and transcellular flux of Bestatin, a dipeptide-like anticancer agent. When added to the apical surface of Caco-2 monolayers grown on microporous membrane filters, Bestatin was accumulated in the cells and was transported unidirectionally to the basolateral side. The cellular uptake of Bestatin from the basolateral as well as from the apical surface was inhibited by excess dipeptides. Bestatin accumulation from the apical surface was dependent on the pH of the incubation medium with an optimal pH of 6.0, whereas uptake from the basolateral surface was insensitive to the medium pH. Kinetic parameters for Bestatin uptake also indicated that the basolateral and apical dipeptide transporters could be distinguished from each other. A sulfhydryl reagent, p-chloromercuribenzene sulfonate, inhibited Bestatin accumulation from both surfaces, although the inhibitory effect on the basolateral transport was greater than that on the apical transport. These findings suggest not only that dipeptide transporters exist on both the apical and basolateral membranes of Caco-2 cells but also that the basolateral dipeptide transporter is distinct from the apical H(+)-dipeptide cotransporter.

4-Chloromercuribenzenesulfonate↗