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1.
Smith HK Beckett RP Clements JM Doel S East SP Launchbury SB Pratt LM Spavold ZM Thomas W Todd RS Whittaker M 《Bioorganic & medicinal chemistry letters》2002,12(24):8039-3599
A series of analogues of the potent peptide deformylase (PDF) inhibitor BB-3497 containing alternative metal binding groups was synthesised. Enzyme inhibition and antibacterial activity data for these compounds revealed that the bidentate hydroxamic acid and N-formyl hydroxylamine structural motifs represent the optimum chelating groups on the pseudopeptidic BB-3497 backbone. 相似文献
2.
East SP Beckett RP Brookings DC Clements JM Doel S Keavey K Pain G Smith HK Thomas W Thompson AJ Todd RS Whittaker M 《Bioorganic & medicinal chemistry letters》2004,14(1):59-62
A series of analogues of the peptide deformylase (PDF) inhibitor BB-3497 where the P3' amide bond was replaced with a ketone functionality is described. The in vitro antibacterial profiling of these compounds revealed that they demonstrate activity against pathogens associated with respiratory tract infections. 相似文献
3.
Davies SJ Ayscough AP Beckett RP Clements JM Doel S Pratt LM Spavold ZM Thomas SW Whittaker M 《Bioorganic & medicinal chemistry letters》2003,13(16):2715-2718
Structural modifications to the peptide deformylase inhibitor BB-3497 are described. In this paper, we describe the initial SAR around this lead for modifications to both the P2' and P3' side chains. Enzyme inhibition and antibacterial activity data revealed that a variety of substituents are tolerated at the P2' and P3' positions of the inhibitor backbone. The data from this study highlights the potential for modification at the P2' and P3' positions to optimise the physicochemical properties. 相似文献
4.
Davies SJ Ayscough AP Beckett RP Bragg RA Clements JM Doel S Grew C Launchbury SB Perkins GM Pratt LM Smith HK Spavold ZM Thomas SW Todd RS Whittaker M 《Bioorganic & medicinal chemistry letters》2003,13(16):2709-2713
Structural modifications to the peptide deformylase inhibitor BB-3497 are described. In this paper, we describe the initial SAR around this lead for modifications to the methylene spacer and the P1' side chain. Enzyme inhibition and antibacterial activity data revealed that the optimum distance between the N-formyl hydroxylamine metal binding group and the P1' side chain is one unsubstituted methylene unit. Additionally, lipophilic P1' side chains that closely mimic the methionine residue in the substrate provided compounds with the best microbiological profile. 相似文献
5.
Van Aller GS Nandigama R Petit CM DeWolf WE Quinn CJ Aubart KM Zalacain M Christensen SB Copeland RA Lai Z 《Biochemistry》2005,44(1):253-260
Polypeptide deformylase (PDF) is an essential bacterial metalloenzyme responsible for the removal of the N-formyl group from the N-terminal methionine of nascent polypeptides. Inhibition of bacterial PDF enzymes by actinonin, a naturally occurring antibacterial agent, has been characterized using steady-state and transient kinetic methods. Slow binding of actinonin to these enzymes is observed under steady-state conditions. Progress curve analysis is consistent with a two-step binding mechanism, in which tightening of the initial encounter complex (EI) results in a final complex (EI*) with an extremely slow, but observable, off-rate (t(1/2) for inhibitor dissociation >or=0.77 days). Stopped-flow measurement of PDF fluorescence confirms formation of EI and provides a direct measurement of the association rate. Rapid dilution studies establish that the potency of actinonin is enhanced by more than 2000-fold upon tightening of EI to form EI*, from K(i) = 530 nM (EI) to Ki*相似文献
6.
Influence of a Brassinosteroid Analogue on Antioxidant Enzymes in Rice Grown in Culture Medium with NaCl 总被引:6,自引:0,他引:6
We studied the effects of a polyhydroxylated spirostanic brassinosteroid analogue (BB-16) on the activities of antioxidant
enzymes in rice seedlings grown in vitro in culture medium supplemented with NaCl. Seedlings were grown in medium with 75 mM NaCl and 0.001 or 0.01 mg dm−3 BB-16 for 16 d or 3-d-old seedlings were exposed for 4 d to 0, 0.001 or 0.01 mg dm−3 BB-16 then further grown in medium with 75 mM NaCl without BB-16. Seedlings exposed to 0.01 mg dm−3 BB-16 for 16 d showed significant increase in the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione
reductase (GR) and a slight increase in ascorbate peroxidase (APX). On the other hand, 4-d exposure to BB-16 only increased
SOD and CAT activities at concentration 0.001 mg dm−3. GR activity was not altered by this BB-16 treatment. These results indicated that BB-16, which is structurally modified
in the lateral chain in relation to natural brassinosteroids, changes the activity of key antioxidant enzymes, which might
confer tolerance to saline stress.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
7.
Selective induction of B7/BB-1 on interferon-gamma stimulated monocytes: a potential mechanism for amplification of T cell activation through the CD28 pathway. 总被引:19,自引:0,他引:19
The B cell activation antigen B7/BB-1 is the natural ligand for the T cell antigen CD28 and these two molecules are capable of mediating T-B cell adhesion. Engagement of the CD28 pathway provides a costimulatory signal to T cells leading to enhanced lymphokine production. We report that interferon-gamma (INF-gamma) induces the expression of B7/BB-1 on monocytes. This induction was very specific since other cytokines and stimuli which activate monocytes including M-CSF, GM-CSF, IL3, TNF-alpha, and LPS were unable to induce B7/BB-1. Following culture of monocytes with INF-gamma, maximal mRNA and cell surface B7/BB-1 expression was detected at 12 and 24 hr, respectively. In addition to antigen presentation, optimal T cell activation and lymphokine synthesis require an additional cell to cell contact signal provided by the antigen presenting cell. The induction of B7/BB-1 on monocytes and subsequent heterophilic interaction of B7/BB-1 with CD28 may provide a mechanism for the amplification of T cell proliferation and lymphokine production by INF-gamma activated monocytes. 相似文献
8.
B lymphoblast antigen (BB-1) expressed on Epstein-Barr virus-activated B cell blasts, B lymphoblastoid cell lines, and Burkitt's lymphomas 总被引:32,自引:0,他引:32
Two new cell surface antigens expressed on B lymphoblastoid cell lines (B-LCL) were defined with cytotoxic mouse monoclonal antibodies. One marker, BB-1 (for B lymphoblast antigen-1), was detected on human and nonhuman primate B-LCL, Epstein-Barr virus (EBV)-activated B cell blasts, most Burkitt's lymphomas, and Ia+ B lymphoblast-like myelomas. Polyclonal B cell activators such as pokeweed mitogen (PWM) and lipopolysaccharide (LPS) also induced the expression of BB-1 on immunoglobulin (Ig)-positive cells. In contrast, BB-1 could not be detected on normal lymphoid tissues by complement-dependent cytotoxicity and immunofluorescence (IF) assays or by analysis with a fluorescence-activated cell sorter (FACS). T cell blasts, T cell leukemias, and pre-B cell or erythroblastic leukemia cell lines were also BB-1 negative. Of particular interest was the finding that BB-1 was expressed on the Jijoye lymphoma but only marginally on a subline of Jijoye, P3HR-1, that lacks receptors for EBV and produces a defective virus incapable of transforming lymphocytes. A second lymphoblast antigen (LB-1) unlike BB-1, was present on both T and B cell blasts and virus-transformed T- and B-LCL but not on normal lymphoid tissues. 相似文献
9.
BB-83698 is a first potent inhibitor of peptide deformylase in this novel class to enter clinical trials. In this study, automated docking, molecular dynamics simulation and binding free energy calculations with the linear interaction energy (LIE) method are first applied to investigate the binding of BB-83698 to the peptide deformylase from Bacillus stearothermophilus. The lowest docking energy structure from each cluster is selected as different representative binding modes. Compared with the experimental data, the results show that the binding of BB-83698 in Mode 1 is the most stable, with a binding free energy of -41.35 kJ/mol. The average structure of the Mode 1 complex suggests that inhibitor interacts with Ile59 and Gly109 by hydrogen bond interaction and with Pro47, Pro57, Ile59 and Leu146 by hydrophobic interaction are essential for the activity of BB-83698. Mode 2 represents a new binding mode. Additionally, if the hydrophilic group is introduced to the benzo-[1,3]-dioxole ring, the binding affinity of BB-83698 to the peptide deformylase from B. stearothermophilus will be greatly improved. 相似文献
10.
Using anti-human B cell monoclonal antibodies prepared against B1 (CD20), B2 (CD21), B4 (CD19), and BB-1 (B lymphoblast antigen-1), we compared the expression of B cell differentiation antigens on a Jijoye-P3HR-1 cell line family of Burkitt's lymphomas. The expression of BB-1 and B2 antigens was faint on P3HR-1 K cell line which is an Epstein-Barr virus (EBV) high producer. On the other hand, B1 and B4 antigens were strongly expressed on it. It was also found that BB-1 expression decreased on P3HR-1 cells after activation of intracellular EBV genes by treating chemically with tumor-promoting agent (TPA) and n-butyrate, or on Raji cells on superinfection with EBV. This decrease of BB-1 was blocked by the additional treatment with retinoic acid, an inhibitor of virus replication. Dual immunofluorescence staining analysis showed that the individual cell expressing EBV-associated antigens expressed BB-1 antigen only marginally. The relationship between the change in phenotypes of host B cells and the activation of the EBV genome is discussed. 相似文献
11.
Production of High-Viscosity Whey Broths by a Lactose-Utilizing Xanthomonas campestris Strain 总被引:2,自引:1,他引:1
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Xanthomonas campestris BB-1L was isolated by enrichment and selection by serial passage in a lactose-minimal medium. When BB-1L was subsequently grown in medium containing only 4% whey and 0.05% yeast extract, the lactose was consumed and broth viscosities greater than 500 cps at a 12 s−1 shear rate were produced. Prolonged maintenance in whey resulted in the loss of the ability of BB-1L to produce viscous broths in whey, indicating a reversion to preferential growth on whey protein, like the parent strain. 相似文献
12.
We report the generation and immune regulation of mice that are deficient in CD28 and 4-1BB (CD137) genes. These mice were viable, fertile and did not display any overt abnormalities and had a normal T cell phenotype in thymus and spleen. Proliferative responses to anti-CD3 and ConA were enhanced in 4-1BB-/- but not in either CD28-/- or double mutant mice, while levels of interleukin-2 were decreased in all mutant mice. Although the 4-1BB-/- mice displayed increased basal levels of most immunoglobulin isotypes tested, the plateau levels of immunoglobulin G2a, immunoglobulin G2b and immunoglobulin A were particularly high compared to wild type controls. The immunoglobulin class switch to T-dependent antigen was normal in 4-1BB-/- mice but was greatly affected in both CD28-/- and 4-1BB-/- CD28-/- mice. Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability was differentially reduced in all mutant mice. Contact sensitivity to allergens showed marginal but not significant change in ear thickness in 4-1BB-/- mice, but an ability to mount contact hypersensitivity to the same antigens was greatly curtailed in CD28-/- and double mutant mice. 相似文献
13.
Immunomodulating potential of supplementation with probiotics: a dose-response study in healthy young adults 总被引:1,自引:0,他引:1
Christensen HR Larsen CN Kaestel P Rosholm LB Sternberg C Michaelsen KF Frøkiaer H 《FEMS immunology and medical microbiology》2006,47(3):380-390
Certain probiotic microorganisms have been found beneficial in the treatment of immune-related diseases and may also affect immune function in healthy people. Intervention studies of probiotics in healthy humans are urgently required. Here, the immunomodulating potential of Bifidobacterium animalis ssp. lactis (BB-12) and Lactobacillus paracasei ssp. paracasei (CRL-431) was studied in a double-blind placebo-controlled parallel dose-response trial (n=71) based on five randomly assigned groups of young healthy adults supplemented for 3 weeks with 0, 10(8), 10(9), 10(10) and 10(11) CFU day(-1), respectively, of a mixture of BB-12 and CRL-431. No statistically significant dose-dependent effect was found for phagocytic activity in blood leukocytes, fecal immunoglobulin A (IgA) concentrations or production of interferon-gamma and interleukin-10 in blood cells. When evaluating data according to the amount of viable BB-12 recovered from faeces, the interferon-gamma production in blood cells was significantly reduced. In conclusion, no solid effect on the immune function of young healthy adults supplemented with even high doses of B. animalis ssp. lactis BB-12 and L. paracasei ssp. paracasei CRL-431 was demonstrated in this study. 相似文献
14.
Gilad O Hjernø K Østerlund EC Margolles A Svensson B Stuer-Lauridsen B Møller AL Jacobsen S 《Journal of Proteomics》2012,75(4):1190-1200
Bifidobacterium animalis subsp. lactis BB-12 is a widely used probiotic strain associated with a variety of health-promoting traits. There is, however, only limited knowledge available regarding the membrane proteome and the proteins involved in oligosaccharide transport in BB-12. We applied two enrichment strategies to improve the identification of membrane proteins from BB-12 cultures grown on glucose and on xylo-oligosaccharides, the latter being an emerging prebiotic substrate recently reported to be fermented by BB-12. Our approach encompassed consecutive steps of detergent- and carbonate-treatment in order to generate inside-out membrane vesicles and to interfere with binding of membrane-associated proteins to the membrane, respectively. Proteins in the enriched membrane fraction and membrane-associated fraction were digested by lysyl endopeptidase and trypsin followed by peptide sequencing by LC-ESI-Q-TOF MS/MS. Ninety of a total of 248 identified unique proteins were predicted to possess transmembrane segments (TMSs), and 56 of these have more than one TMS. Seventy-nine of the identified proteins are annotated to be involved in transport of amino acids, oligosaccharides, inorganic ions, nucleotides, phosphate or exopolysaccharides, or to belong to the F1F0-ATP-synthetase complex and the protein translocation machinery, respectively. 相似文献
15.
B Ehlin-Henriksson E A Clark V J?nsson G Klein 《Journal of immunology (Baltimore, Md. : 1950)》1983,130(5):2448-2452
In the Jijoye-P3HR-1 family of Burkitt lymphoma sublines, the expression of the B lymphoblast-1 antigen, BB-1, identified by the monoclonal antibody described by Yokochi and colleagues, was found to be strictly related to the expression of the EBV receptor/C3 receptor (EBVR/C3R) complex. It was absent on the receptor-negative P3HR-1 line, present in the original receptor-positive Jijoye line, and reappeared in nonvirus producer sublines derived from P3HR-1 itself. We suggest the BB-1 antigen is related to the EBVR/C3R complex in the Jijoye family, either at the level of genetic or epigenetic determination or at the level of steric interaction on the cell membrane. In all probability, however, the BB-1 antigen is not identical to the receptor itself. It is also clear that a similar relationship does not necessarily apply to other cell lines. In the course of the studies, it was accidentally discovered that propagation of the P3HR-1 cells on newborn instead of fetal calf serum induces the concomitant expression of EBV receptors, C3 receptors, and the BB-1 antigen. The mechanism of this induction is obscure; it does not appear to be related to any significant change in the frequency of virus-producing cells. 相似文献
16.
In this study, 13 bifidobacterial strains were tested for
their ability to adhere to immobilized extracellular matrix (ECM) proteins.
Only two Bifidobacterium adolescentis strains adhered to immobilized
type I and type V collagens, but not to laminin, fibronectin, and type III
and IV collagens. The adhesion of B. adolescentis BB-119 to
type V collagen was inhibited by type I and V collagens and gelatin, and was
diminished after protease treatment of the cells. Periodate treatment of
immobilized collagen and the presence of galactose inhibited the adhesion of
strain BB-119 to type V collagen. Two cell surface proteins with molecular
masses of 36 kDa and 52 kDa from strain BB-119 were found to bind to
horseradish peroxidase-conjugated type V collagen by ligand blotting. We
concluded that B. adolescentis BB-119 binds to type V
collagen at galactose chains as target via these two cell surface proteins by
their lectin-like activity.
Received: 15 October 1996 / Accepted: 20 November 1996 相似文献
17.
Matrix metalloproteinases and lysosomal cysteine proteases in osteoclasts contribute to bone resorption through distinct modes of action 总被引:1,自引:0,他引:1
Inui T Ishibashi O Origane Y Fujimori K Kokubo T Nakajima M 《Biochemical and biophysical research communications》1999,258(1):173-178
The effects of inhibitors of matrix metalloproteinases (MMPs) and lysosomal cysteine proteases on osteoclastic pit formation in dentine slices were investigated. A nonspecific cysteine protease inhibitor, E-64, inhibited pit formation on naked slices in a concentration-dependent manner, and at 10 microM E-64 reduced the pit volume by 70%. However, up to 10 microM of the MMP inhibitor, BB-94, did not show any inhibition of pit formation. On the other hand, on slices coated with reconstituted basement membrane, both BB-94 and E-64 at 10 microM showed a marked decrease in pit volume by 73% and 68%, respectively. By a combination of treatment with both BB-94 and E-64, pit formation could be completely suppressed. These results suggest that MMPs are necessary for the migration of precursor and/or immature osteoclasts to bone surface through basement membranes, while cysteine proteases are essential for the osteoclastic degradation of bone collagen. 相似文献
18.
目的:研究培养条件对吡虫啉杀虫剂降解菌苍白杆菌BB -1(Ochrobactum sp.BB -1)生长的影响.方法:采用超声波破碎菌体细胞得到粗酶液;应用单因素试验研究培养条件对吡虫啉杀虫剂降解菌 Ochrobactum BB -1生长的影响.结果:降解酶定域试验表明,BB -1吡虫啉降解酶属于胞内蛋白组分.适合Ochrobactum BB -1生长的最佳碳、氮源分别是甘露醇和酵母膏,浓度分别为30g/L和16g/L;最适培养条件为pH 7.0,250mL三角瓶培养基装液量70mL,培养温度30℃.结论:苍白杆菌BB -1(Ochrobactum BB -1)生长条件要求简单,适于进一步研究其对吡虫啉杀虫剂的降解性能. 相似文献
19.
P. G. Varley A. J. Brown H. C. Dawkes N. R. Burns 《European biophysics journal : EBJ》1997,25(5-6):437-443
Analytical ultracentrifugation (AUC) has re-emerged as a powerful technique for protein characterisation. We report the pivotal
role sedimentation equilibrium AUC has played in the development of macrophage inflammatory protein-1α (MIP-1α) as a protein therapeutic. MIP-1α has potential clinical applications in cancer but its clinical use is limited, since it associates to form large insoluble
aggregates in physiological buffers. Using AUC as a screening technique, we have produced a biologically active variant of
MIP-1α, BB-10010, which has a reduced tendency to aggregate in physiological buffers. The aggregation of protein based pharmaceuticals
is routinely monitored by size exclusion chromatography (SEC). Comparison of the data acquired by SEC and AUC, demonstrates
that owing to the complexity of BB-10010, AUC analysis is required in addition to SEC to provide a rigorous characterisation
of molecular association. This work has been extended to include the use of AUC as an analytical tool to monitor the quality
of BB-10010 during formulation and stability studies.
Accepted: 6 October 1996 相似文献
20.
Effect of Spirostane Analogues of Brassinosteroids on Callus Formation and Plant Regeneration in Lettuce (Lactuca sativa) 总被引:1,自引:0,他引:1
M. Núñez W.J. Siqueira M. Hernández M.A.T. Zullo C. Robaina F. Coll 《Plant Cell, Tissue and Organ Culture》2004,78(1):97-99
Two spirostane analogues of brassinosteroids (BB-6 and MH-5) were tested for callus induction and plant regeneration in lettuce.
They were used as a cytokinin (6-BA) substitute or in combination with 6-BA at different concentrations. Treatment with 0.1
mg l−1 6-BA was used as control. Results showed that there was no callus induction when 6-BA was substituted by these analogues.
However, BB-6 and MH-5 enhanced both callus formation and shoot regeneration from cotyledons in lettuce when added at determined
concentrations with 0.1 mg l−1 of 6-BA in the culture medium. 相似文献