Disease relevance of benzenecarboximidamide

• By means of reconstitution experiments with highly purified variants of P-450 IIC3 from rabbit liver and with purified variants of P-450 IIC expressed by recombinant Escherichia coli, the participation of the two variants P-450 IIC3 (6 beta H) and P-450 IIC3 (6 beta L) in the N-hydroxylation of benzamidine was unequivocally confirmed [1].
• A series of benzamidine isoxazoline derivatives was evaluated for their inhibitory potency against purified human factor Xa (fXa) and in a rabbit model of arteriovenous shunt thrombosis for their antithrombotic activities, expressed as K(I) and IC(50), respectively [2].
• Extraction from mastocytoma homogenates at high ionic strength, followed by gel filtration and benzamidine affinity chromatography yielded a product with several closely spaced bands (Mr 30,000-32,000) on gel electrophoresis and a single N-terminal sequence [3].
• We assayed several benzamidine derivatives for inhibition potency with HRgpA and RgpB gingipains, enzymes which are involved in the pathogenesis of gingivitis and periodontal disease [4].
• Comparison with benzamidine complement-inhibitory activity models and with benzene derivatives toxicity models from the literature favors our novel approach [5].

Psychiatry related information on benzenecarboximidamide

• Here we investigate one such case and report the association free energy profile (potential of mean force) between trypsin and benzamidine along a chosen reaction coordinate as calculated using the grand canonical Monte Carlo method [6].

High impact information on benzenecarboximidamide

• This conversion was also inhibited by pretreatment with the serine protease inhibitor benzamidine (10 mM) but not the cysteine protease inhibitor E64 (100 microM) [7].
• In contrast, treating von Willebrand factor with neuraminidase and beta-galactosidase in the presence of protease inhibitors (20 mM benzamidine, 20 U/ml aprotonin, 15 micrograms/ml leupeptin) resulted in a comparable removal of carbohydrate with no change in ristocetin cofactor activity [8].
• 2. The trypsin inhibitor benzamidine was found to inhibit the yolk proteinase in vivo [9].
• The release of radioactivity was partially inhibited by protease inhibitors, including alpha 2-macroglobulin, leupeptin, and benzamidine, but the negative fluorescent spots appeared unaffected by any of these inhibitors [10].
• (iii) Both cyclin A cleavage activity and OmpT activity are heat stable, resistant to denaturation, and inhibited by Zn(2+), Cu(2+), or benzamidine [11].

Biological context of benzenecarboximidamide

• Arginine and benzamidine, ligands known to specifically bind to the kringle 5 domain of plasminogen, blocked the binding of thrombospondin to plasminogen [12].
• The benzamidine crystals possess a freely accessible active site and are hence well suited for soaking small molecules, facilitating the improvement of inhibitors [13].
• The actions of tryptase on HUVEC were inhibited by heat inactivation of the enzyme, or by preincubating with the protease inhibitors leupeptin or benzamidine, suggesting a requirement for an intact catalytic site [14].
• Benzamidine, a competitive and reversible inhibitor of trypsin, also inhibited the glycosylation of IgE-binding factors by GEF [15].
• KI values for benzamidine of 0.50 +/- 0.05 mM and 0.23 +/- 0.02 mM were obtained for S-2251 hydrolysis, as catalyzed by alpha 2M-plasmin and plasmin, respectively [16].

Anatomical context of benzenecarboximidamide

• Both Ag-specific GEF and nonspecific GEF from the hybridoma bind to p-aminobenzamidine-agarose, and are recovered by elution with benzamidine [17].
• Porcine ileal mucosa was homogenized and freeze-thawed in 0.05 M NH4HCO3 + 0.01 M EDTA + 1 mM benzamidine hydrochloride at pH 8 [18].
• Leupeptin and benzamidine inhibited tryptase-induced fibroblast proliferation (P < 0.05), and SLIGKV mimicked tryptase's effect [19].
• The addition of benzamidine, a noncompetitive synthetic trypsin inhibitor, to semen samples has kept a portion of the sperm phospholipase A2 (PA2) in its zymogen form and allowed its isolation after acid extraction [20].
• In the present work, we have studied the membrane crystallization process of benzamidine inhibited trypsin from bovine pancreas (BPT), with ammonium sulphate (dissolved in Tris-HCl buffer, 0.1 M, pH 8.5), as precipitant agent [21].

Associations of benzenecarboximidamide with other chemical compounds

• As demonstrated using the protease inhibitor benzamidine and by specific active site inhibition with 1,5-dansyl-Glu-Gly-Arg chloromethyl ketone, both FVIIa and FXa lost their ability to elicit a calcium response when devoid of their proteolytic activity [22].
• The isolation method utilized benzamidine to inhibit the premeture activation of the zymogen and included pH precipitation, ammonium sulfate fractionation, and sodium chloride precipitation [23].
• Pentamidine binds QacR in a novel fashion whereby one of its benzamidine groups interacts with residue Glu-63, and the other is neutralized by carbonyl and side chain oxygen atoms [24].
• Conversion by the particulate enzyme was inhibited by benzamidine or chloroquine, but not by pancreatic trypsin inhibitor, indicating its dissimilarity to trypsin [25].
• Refined 2.3 A X-ray crystal structure of bovine thrombin complexes formed with the benzamidine and arginine-based thrombin inhibitors NAPAP, 4-TAPAP and MQPA. A starting point for improving antithrombotics [26].

Gene context of benzenecarboximidamide

• Because crystals of the uPA/benzamidine complex allow inhibitor exchange by soaking procedures, the structure-based design of new generations of uPA inhibitors can rely on the assistance of x-ray analysis [27].
• The refined crystal structure of bovine beta-trypsin at 1.8 A resolution. II. Crystallographic refinement, calcium binding site, benzamidine binding site and active site at pH 7.0 [28].
• Here we report the X-ray structure of human trypsin IV in complex with the inhibitor benzamidine at 1.7 A resolution [29].
• Only 3-4 dichloroisocoumarin and benzamidine inhibited purified PAP [30].
• The overall conformation of plasminogen depends upon the presence of anions and molecules such as AHA (6-aminohexanoic acid) and BZ (benzamidine) [31].

Analytical, diagnostic and therapeutic context of benzenecarboximidamide

• A bound molecule of benzamidine, which was essential for crystallization and is also found in the hinge region, appears to reduce flexibility between the two domains [32].
• Western blot analysis following SDS-PAGE of the proteins of the FE isolated in the presence of hMW-SBTI and benzamidine revealed the presence of the 350/320-kDa proteins which cross-reacted with anti-receptor antibody [33].
• The two-way and three-way interactions among active-site-blocked bovine thrombin, bovine protein C, and the elastase fragment of rabbit thrombomodulin (elTM) were examined by analytical ultracentrifugation at 23.3 degrees C in 100 mM NaCl, 50 mM Tris (pH 7.65), and 1 mM benzamidine, in the presence of 0 to 5 mM calcium chloride [34].
• However, NAPAP and other benzamidine derivatives do not show favorable pharmacological properties; above all, they have very low systemic bioavailability after oral administration [35].
• The binding of a tetrazole to an N,N'-diethyl-substituted benzamidine has been studied for the first time by X-ray crystallography, solution NMR methods, and electrospray mass spectrometry [36].

References