Disease relevance of Piperazinedione

• The present study was designed to test the interaction between a nonantibody, nonpeptide, diketopiperazine-based inhibitor of PAI-1, XR5118, and PAI-1 and to assess the effect of XR5118 on PAI-1 activity in vitro and on in vivo thrombolysis and thrombus growth in an experimental thrombosis model in rabbits [1].
• Piperazinedione, total body irradiation, and autologous bone marrow transplantation in chronic myelogenous leukemia [2].
• Eleven patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in blast crisis (ten patients) or accelerated disease (one patient) were treated with piperazinedione (PIP) and fractionated total body irradiation (TBI) followed by autologous bone marrow transplantation (ABMT) [2].
• These studies confirm and extend the neuroprotective effects of this diketopiperazine in traumatic brain injury [3].
• Albonoursin [cyclo(deltaPhe-DeltaLeu)], an antibacterial peptide produced by Streptomyces noursei, is one of the simplest representatives of the large diketopiperazine (DKP) family [4].

Psychiatry related information on Piperazinedione

• Both TRH and TRH-OH caused dose dependent increases in locomotor activity, whereas DKP and the two analogues had no effect [5].

High impact information on Piperazinedione

• Nevertheless, hTycA is recognized by the next proline-activating elongation module TycB1 in vitro, and the dipeptide is formed and released as diketopiperazine [6].
• A study of the subcellular distribution of histidyl-proline diketopiperazine and thyrotropin-releasing hormone suggests that the releasing factor is concentrated in synaptosomal vesicles while the diketopiperazine is not [7].
• GliP, a Multimodular Nonribosomal Peptide Synthetase in Aspergillus fumigatus, Makes the Diketopiperazine Scaffold of Gliotoxin [8].
• Biochemical mechanism of action of a diketopiperazine inactivator of plasminogen activator inhibitor-1 [9].
• High diastereospecificity for PDE5 inhibition was observed in the piperazinedione series with the cis-(6R,12aR) enantiomer displaying the highest PDE5 inhibitory activity [10].

Chemical compound and disease context of Piperazinedione

• We have cloned and sequenced DNA from Escherichia coli that, when present in a high-copy-number plasmid, confers resistance to the diketopiperazine antibiotic, bicyclomycin (Bc) [11].
• Intracerebroventricular diketopiperazine (50 micrograms), a TRH metabolite, and RX77368 (50 micrograms), a TRH analogue, also potentiated swim (21 degrees C) analgesia, effects also independent of hypothermia and basal reactivity to pain [12].
• Toxicity of aspartame and its diketopiperazine for Wistar rats by dietary administration for 104 weeks [13].
• We conclude that the addition of piperazinedione to cyclophosphamide plus DTIC does not improve the response rate in patients with metastatic malignant melanoma [14].

Biological context of Piperazinedione

• To overcome the BCRP-mediated drug resistance, the fungal secondary metabolite TPS-A, a diketopiperazine, was analyzed with regard to its potency to reverse the BCRP-mediated drug-resistant phenotype [15].
• For optimum results, the oxidation should be carried out prior to diketopiperazine cyclization [16].
• Using primary neuronal cultures, three novel dipeptides were compared to the previously reported diketopiperazine as well as to vehicle controls; each of the compounds reduced cell death after direct physical trauma or trophic withdrawal [17].
• Kinetics of diketopiperazine formation using model peptides [18].
• Structure-activity relationship of a bitter diketopiperazine revisited [19].

Anatomical context of Piperazinedione

• The cytotoxicity, mutagenicity, and DNA damaging potential of trans-cyclopropylbis (diketopiperazine) (3) and chelating agents related to ICRF 159 (1) were examined as a function of concentration and duration of exposure in the Chinese hamster cell line V79A [20].
• The effect of piperazinedione on hemopoietic stem cells is short in duration (nadir day 1) [21].
• The detection of His-Pro diketopiperazine among the metabolites was of special interest since this biologically active metabolite was also found in the pancreas as an endogenous peptide and reported to be either a TRH degradation product or derived from sources other than just TRH [22].
• Although c(Dmt-Tic) exhibited a weak antagonist activity with mouse vas deferens, this diketopiperazine may provide a scaffolding for the formation of more potent antagonists for potential therapeutic applications [23].
• In vitro production of a TRH-homologous peptide and His-Pro diketopiperazine by human semen [24].

Associations of Piperazinedione with other chemical compounds

• The self-condensation of 2'(3')-O-glycyl esters of adenosine, adenosine-5'-(O-methylphosphate) and P1, P2-diadenosine-5'-pyrophosphate in 6.2 mM solutions at pH 8.0 and -5 degrees C in the presence of 12.5 mM poly(U) yields approximately 3 times as much diketopiperazine as reactions without poly(U) [25].
• Binding of [125I]iodo-Tyr1-SRIF is not inhibited by morphine, beta-endorphin, [D-Ala2]Met-enkephalin, LHRH, TRH, histidylproline diketopiperazine, neurotensin, substance P, bombesin or vasoactive intestinal peptide [26].
• The diketopiperazine "C5" conformational mimic has been incorporated into the L-prolyl-L-leucylglycinamide (PLG, 1) structure and into the bicyclic lactam PLG peptidomimetic structure 3 to give compounds 5 and 6, respectively [27].
• We have previously shown that a diketopiperazine structurally related to the TRH metabolite cyclo-his-pro reduces neuronal cell death in vitro and in vivo [17].
• Barettin (cyclo [(6-bromo-8-en-tryptophan) arginine]), a diketopiperazine isolated from the marine sponge Geodia barretti, is a potent inhibitor of barnacle larvae settlement with an EC50-value of 0.9 microM [28].

Gene context of Piperazinedione

• Reversal of P-glycoprotein-mediated multidrug resistance by XR9051, a novel diketopiperazine derivative [29].
• We report here the evaluation of three diketopiperazine-based low molecular weight inhibitors of PAI-1 activity (XR334, XR1853 and XR5082) [30].
• XR5967, a diketopiperazine, dose-dependently inhibited the activity of human and murine PAI-1, towards urokinase plasminogen activator (uPA), with IC50 values of 800 nM and 8.3 microM, respectively [31].
• Similar treatment of the parent compound I with DCC led to a self-condensation reaction giving a diketopiperazine VI [32].
• Novel CCK-B receptor agonists: diketopiperazine analogues derived for CCK4 bioactive conformation [33].

Analytical, diagnostic and therapeutic context of Piperazinedione

• 24 cases of adult acute leukaemia, of which 21 were evaluable, were treated in irreversible relapse with high-dose piperazinedione and supralethal total-body irradiation (T.B.I.) in conjunction with autologous marrow transplantation (A.B.M.T.). The grafted marrow cells had been collected and stored in liquid nitrogen at the time of remission [34].
• Circular dichroism and absorbance properties of nitrotyrosyl chromophores in staphylococcal nuclease and in a model diketopiperazine [35].
• From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT) [36].
• Studies were conducted to evaluate the effect of piperazinedione on hemopoietic stem cells and the recovery of hemopoiesis after syngeneic transplantation [21].
• A diketopiperazine forming linker allowed cleavage of peptides into aqueous buffer which, without further purification, could be used immediately in cell culture assays [37].

References