nitrobestatin and ubenimex

nitrobestatin has been researched along with ubenimex* in 5 studies

Other Studies

5 other study(ies) available for nitrobestatin and ubenimex

ArticleYear
Characterization of a cytosolic aminopeptidase from Encephalitozoon intestinalis.
    Parasitology, 2002, Volume: 124, Issue:Pt 1

    Aminopeptidase activity was detected in Encephalitozoon intestinalis using a fluorometric assay. The aminopeptidase was capable of hydrolysing different amino acids bound to 7-amino-4-trifluoromethyl coumarin, with maximal activity against the amino acid, leucine. Aminopeptidase activity was localized in E. intestinalis spores and in intracellular stages. Enzymatic activity was inhibited by the traditional aminopeptidase inhibitors, bestatin and its analogue, nitrobestatin. Inhibition with the chelating agents, EDTA and 1,10-phenanthroline, suggested that the enzyme activity belongs to the metalloaminopeptidase class. Subcellular fractionation demonstrated that maximal enzyme activity was localized in the cytosolic fraction. Direct fluorogenic substrate analysis by native polyacrylamide gel electrophoresis estimated a molecular weight of 70.8 kDa. Direct fluorogenic analysis by polyacrylamide ampholyte gel electrophoresis indicated an isoelectric point of 4.8. The enzyme was both heat (> 37 degrees C) and cold (< 0 degrees C) labile with an optimal activity at pH 7.2. This is the first report characterizing a cytosolic aminopeptidase in microsporidia.

    Topics: Animals; Chelating Agents; Coumarins; Edetic Acid; Encephalitozoon; Fluorometry; Humans; Isoelectric Point; Leucine; Leucyl Aminopeptidase; Molecular Weight; Phenanthrolines; Protease Inhibitors; Substrate Specificity

2002
In vitro and in vivo evaluation of aminopeptidase inhibitors as antimicrosporidial therapies.
    The Journal of eukaryotic microbiology, 2001, Volume: Suppl

    Topics: Aminopeptidases; Animals; Anti-Bacterial Agents; Cyclohexanes; Disease Models, Animal; Encephalitozoon cuniculi; Encephalitozoonosis; Enzyme Inhibitors; Fatty Acids, Unsaturated; Female; Leucine; Mice; Mice, Nude; O-(Chloroacetylcarbamoyl)fumagillol; Parasitic Sensitivity Tests; Peptides; Sesquiterpenes

2001
The role of aminopeptidases in haemoglobin degradation in Plasmodium falciparum-infected erythrocytes.
    Molecular and biochemical parasitology, 2001, Sep-28, Volume: 117, Issue:1

    Intra-erythrocytic Plasmodium parasites digest host cell haemoglobin and use the liberated amino acids for protein synthesis. Although several endoproteases (aspartic, cysteine, and metallo-) have been shown to be involved in the initial stages of haemoglobin degradation, little is known about the steps immediately before amino acid release. In our studies, fluorometric enzyme assays indicated that the stage of the P. falciparum erythrocytic cycle with highest aminopeptidase activity was the stage at which most haemoglobin degradation occurs, i.e. the trophozoite. Consistent with these results, metabolic growth assays indicated that the late ring/trophozoite stage was most susceptible to aminopeptidase inhibitors. To reconstitute the terminal stages of haemoglobin breakdown in vitro, we synthesised three peptides with amino acid sequences corresponding to known products of the endoproteolytic digestion of haemoglobin and employed them as substrates for aminopeptidases. Both trophozoite cytosolic extract, and partially-purified aminopeptidase, hydrolysed these peptide fragments to amino acids. Hydrolysis appeared to occur sequentially from the amino-termini of the peptides, and was inhibited in a concentration-dependent manner by the aminopeptidase-specific inhibitor nitrobestatin. The results suggest that P. falciparum aminopeptidases could be the enzymes responsible for the hydrolysis of haemoglobin-derived peptides to free amino acids. Lack of ultrastructural change in parasites treated with relevant concentrations of aminopeptidase-specific inhibitors, however, indicated that little feedback exists whereby the inhibition of cytosolic aminopeptidases results in obvious inhibition of initial haemoglobin degradation in the digestive vacuole.

    Topics: Aminopeptidases; Animals; Erythrocytes; Hemoglobins; Humans; Leucine; Malaria, Falciparum; Plasmodium falciparum

2001
Plasmodium chabaudi chabaudi and P. falciparum: inhibition of aminopeptidase and parasite growth by bestatin and nitrobestatin.
    Parasitology research, 1998, Volume: 84, Issue:7

    The major leucine aminopeptidase of the rodent malarial parasite Plasmodium chabaudi chabaudi was partially purified using a combination of high-pressure liquid chromatography on a size-exclusion column and affinity chromatography using the aminopeptidase-specific inhibitor bestatin as the ligand. The purified enzyme showed simple Michaelis-Menten kinetics when the fluorogenic peptide analogue leucyl-7-amino-4-methyl-courmarin served as the substrate, and it was strongly inhibited by both bestatin (Ki = 50.7 +/- 21.0 nM) and nitrobestatin (Ki = 2.51 +/- 0.2 nM) in a competitive manner. These inhibitors were also potent blockers of the growth of P. c. chabaudi and the human parasite P. falciparum in culture, and nitrobestatin was again the more potent. Therefore, the leucine aminopeptidase represents an important target to which novel anti-malarial agents could be directed.

    Topics: Animals; Antimalarials; Dose-Response Relationship, Drug; Leucine; Leucyl Aminopeptidase; Mice; Plasmodium chabaudi; Plasmodium falciparum; Protease Inhibitors

1998
Synthesis and structure-activity relationships of bestatin analogues, inhibitors of aminopeptidase B.
    Journal of medicinal chemistry, 1977, Volume: 20, Issue:4

    Stereoisomers and analogues of bestatin, [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, were synthesized and tested for aminopeptidase B and leucine aminopeptidase inhibiting activity. Among the eight stereoisomers, the 2S stereoisomers exhibited strong activity. In a series of compounds in which the L-leucine residue of bestatin was substituted with other amino acids, only the one containing isoleucine showed more activity than bestatin. Norleucine, norvaline, methionine, valine, serine, glutamine, phenylalanine, glutamic acid, proline, and lysine analogues gave, in that order, decreasing activity. Alkyl and phenyl sub stitution for the benzyl group of bestatin decreased the activity markedly. p-Methyl-, p-chloro-, and p-nitrobestatins showed greater activity than bestatin.

    Topics: Aminopeptidases; Dipeptides; Leucine; Leucyl Aminopeptidase; Stereoisomerism; Structure-Activity Relationship

1977