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  • 1
    Publikationsdatum: 2024-04-01
    Beschreibung: In this study we interrogate 630 compounds of the Maybridge Rule of 3 Fragment Library for compounds that interact with, and inhibit TbCK. The Maybridge Rule of 3 Fragment Library is a small collection of quantifiable diverse, pharmacophoric rich, chemical entities that comply with the following criteria; MW ≤ 300, cLogP ≤ 3, H-Bond Acceptors ≤ 3, H-Bond Donors ≤ 3, Rotatable bonds (Flexibility Index) ≤ 3, Polar Surface Area ≤ 60 Å2 and aqueous solubility ≥ 1 mM using LogS and high purity (≥ 95%). Comparisons between two different screening methods, a coupled enzyme activity assay and differential scanning fluorimetry, has allowed identification of compounds that interact and inhibit the T. brucei choline kinase, several of which possess selective trypanocidal activity. Screening of a comparatively small fragment library by two different screening methods has allowed identification of several compounds that interact with and inhibit TbCK, a genetically validated drug target against African sleeping sickness. Some of the inhibitory fragments were also selectively trypanocidal, considering these are relatively simple molecules with no optimization, finding low μΜ inhibitors is very encouraging. Moreover some of the morphological phenotypes of these trypanocidal compounds include cell-cycle arrests similar to those observed for the TbCK conditional knockout grown under permissive conditions.
    Schlagwort(e): pharmacology ; toxicology ; pharmacology ; toxicology ; Assay ; Enzyme ; Molar concentration ; Protein ; Thermal shift assay ; Trypanosoma brucei ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKG Pharmacology
    Sprache: Englisch
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    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    s.l. : American Chemical Society
    Macromolecules 1 (1968), S. 204-213 
    ISSN: 1520-5835
    Quelle: ACS Legacy Archives
    Thema: Chemie und Pharmazie , Physik
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    s.l. : American Chemical Society
    Journal of medicinal chemistry 13 (1970), S. 1040-1042 
    ISSN: 1520-4804
    Quelle: ACS Legacy Archives
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    ISSN: 1574-695X
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Biologie , Medizin
    Notizen: Much work has focused on trying to identify markers in Helicobacter pylori that might allow the eventual disease outcome of an infection to be predicted. In this study we examined the cagA and vacA genotype, and Lewis status in a panel of 43 Irish H. pylori clinical isolates, and investigated a possible correlation with disease pathology. In addition, differences in the poly-(C) tract of the α(1,3)-fucosyltransferase gene were examined to identify a possible correlation with gene expression. Only three of 43 isolates were cagA-negative, whereas the remaining 40 isolates, independent of pathology, were cagA-positive. In all the strains we examined, the vacA signal-sequence was type s1a. For the vacA mid-region 12/43 isolates were type m1 and 31/43 isolates were type m2. These data, and examination of isolates from different pathology groups, suggests that there is no correlation between virulence and vacA genotype in the Irish population of H. pylori isolates. Western blotting of whole cell lysates from 32 H. pylori isolates showed 3/32 displayed only the Lex epitope, 12/32 only the Ley, 13/32 both epitopes and 4/32 neither epitope. No apparent association between Lewis phenotype and disease pathology was evident. A range of lengths of poly-(C) tract were observed in the α(1,3)-fucosyltransferase gene, however the length of the tract in an isolate did not correlate with the Lewis structures present. We conclude that future studies on H. pylori pathogenesis should not alone focus on the importance of molecular markers, but also on the host response, including genetic background and immune responsiveness.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. S108 
    ISSN: 1432-0827
    Schlagwort(e): Femoral neck ; Fracture ; Bone remodeling
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Hip fracture incidence has shown strong upward secular trends in many societies with wide differences in age adjusted incidence between nations. Falls and reduced physical activity have emerged as the strongest risk factors in epidemiological studies, while clinical investigations have pointed to secondary hyperparathyroidism as an important candidate cause of the loss of femoral cortical bone in old age. Until recently there have been few studies performed directly on the region of interest in the proximal femur. Noninvasive methodology using "Sr has now been developed by our group for measuring bone formation and (with concurrent serial DXA densitometry) resorption in the femoral neck. Bone turnover averaged about 8% annually in controls. A group of younger cases of femoral fracture showed similar indices of total and regional bone formation to a control group; but their resorption was higher. To further investigate this, a femoral neck bone biopsy technique has been developed which can be applied to fracture cases treated by arthroplasty. Preliminary studies have established that the anatomical asymmetry of the neck in cross-section is considerable and imposes restraints on the interpretation of smaller or incomplete femur biopsies. Prospects are quite good that, in the absence of tetracycline pre-labeling, mineralization can be studied by assessment of alkaline phosphatase-positive surfaces in cryostat sections. Moreover, such sections will permit study of other anatomically localized metabolic activities as well as antigen expression and osteocyte viability. Candidate mechanisms for the regional decline in bone quality as well as bone mass in subjects suffering hip fracture can now be investigated more effectively.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    [s.l.] : Nature Publishing Group
    Nature 299 (1982), S. 456-458 
    ISSN: 1476-4687
    Quelle: Nature Archives 1869 - 2009
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Notizen: [Auszug] tRNA was introduced into C. elegans embryos by injection into the hermaphrodite gonad (Fig. 1). In this technique, a mjcropipette penetrates the adult cuticle and body wall to enter the distal arm of the gonadal tube (-400 |xm long and 30 jjon in diameter, Fig. la). This region of the gonad ...
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    facet.materialart.
    Unbekannt
    Macomb, Ill., etc. : Periodicals Archive Online (PAO)
    Journal of Geography. 93:1 (1994:Jan./Feb.) 54 
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Journal of muscle research and cell motility 9 (1988), S. 1-8 
    ISSN: 1573-2657
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary It is now possible to map almost any disease locus to a chromosomal region in the human genome by family studies with restriction fragment length polymorphisms. Duchenne and Becker muscular dystrophies have been shown to be localized within the same small region of Xp21 on the human X chromosome. Myotonic dystrophy has been localized to a region close to the centromere of chromosome 19. Technologies are now available to identify candidate genes for the diseases. Autosomal recessive muscular dystrophies are more difficult to study, but even these will be amenable to analysis in the very near future. The next decade should witness some exciting advances in the molecular analysis and clinical management of human muscular dystrophies.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 278 (1994), S. 629-631 
    ISSN: 1432-0878
    Schlagwort(e): Fibroblasts ; Orbit ; Fine structure ; Graves' disease ; Connective tissue ; Man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The fine structure of cultured human orbital fibroblasts was investigated by transmission electron microscopy. One culture was derived from a patient with severe Graves' ophthalmopathy, the other from a donor without inflammatory orbital disease. Despite their known differences in metabolism, orbital fibroblasts from either source revealed no ultrastructural differences. The cells had extensive thin cytoplasmic processes. The perinuclear areas contained multiple assemblies of Golgi membranes, modest amounts of rough endoplasmic reticulum, intermediate filaments, and lysosome-like structures. Glycogen deposits were noted both in the perinuclear cytoplasm and in the thin processes. These ultrastructural features of orbital fibroblasts are the same as those of fibroblasts from other anatomic regions.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 278 (1994), S. 629-631 
    ISSN: 1432-0878
    Schlagwort(e): Key words: Fibroblasts ; Orbit ; Fine structure ; Graves' disease ; Connective tissue ; Man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract. The fine structure of cultured human orbital fibroblasts was investigated by transmission electron microscopy. One culture was derived from a patient with severe Graves' ophthalmopathy, the other from a donor without inflammatory orbital disease. Despite their known differences in metabolism, orbital fibroblasts from either source revealed no ultrastructural differences. The cells had extensive thin cytoplasmic processes. The perinuclear areas contained multiple assemblies of Golgi membranes, modest amounts of rough endoplasmic reticulum, intermediate filaments, and lysosome-like structures. Glycogen deposits were noted both in the perinuclear cytoplasm and in the thin processes. These ultrastructural features of orbital fibroblasts are the same as those of fibroblasts from other anatomic regions.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
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