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51.
Clones of cytogenetically abnormal cells have been recognized in fibroblasts cultured from normal human adult skin. No such clones have been observed in human embryo skin fibroblasts cultured in the same way. Although the culture conditions may have played some part in the emergence of these clones, it is possible that the abnormal cells from which the clones were derived were present in vivo. 相似文献
52.
Patricia L. M Dahia Ken N Ross Matthew E Wright César Y Hayashida Sandro Santagata Marta Barontini Andrew L Kung Gabriela Sanso James F Powers Arthur S Tischler Richard Hodin Shannon Heitritter Francis Moore Jr. Robert Dluhy Julie Ann Sosa I. Tolgay Ocal Diana E Benn Deborah J Marsh Bruce G Robinson Katherine Schneider Judy Garber Seth M Arum Márta Korbonits Ashley Grossman Pascal Pigny Sérgio P. A Toledo Vania Nosé Cheng Li Charles D Stiles 《PLoS genetics》2005,1(1)
53.
Watts J Benn A Flinn N Monk T Ramjee M Ray P Wang Y Quibell M 《Bioorganic & medicinal chemistry》2004,12(11):2903-2925
A stereoselective synthesis of functionalised (2R,3R)-2,3-dimethyl-3-amidotetrahydrofuran-4-one, its (2S,3R)-epimer and (3aR,6aR)-N-(3-oxo-hexahydrocyclopenta[b]furan-3a-yl)acylamide cysteinyl proteinase inhibitors has been developed using Fmoc-protected scaffolds 6-8 in a solid-phase combinatorial strategy. Within these scaffolds, the introduction of an alkyl substituent alpha to the ketone affords chiral stability to an otherwise configurationally labile molecule. Preparation of scaffolds 6-8 required stereoselective syntheses of suitably protected alpha-diazomethylketone intermediates 9-11, derived from appropriately protected alpha-methylthreonines (2R,3R)-12, (2R,3S)-13 and a protected analogue of (1R,2R)-1-amino-2-hydroxycyclopentanecarboxylic acid 14. Application of standard methods for the preparation of amino acid alpha-diazomethylketones, through treatment of the mixed anhydride or pre-formed acyl fluorides of intermediates 12-14 with diazomethane, proved troublesome giving complex mixtures. However, the desired alpha-diazomethylketones were isolated and following a lithium chloride/acetic acid promoted insertion reaction provided scaffolds 6-8. Elaboration of 6-8 on the solid phase gave alpha,beta-dimethyl monocyclic ketone based inhibitors 38a-f, 39a,b,d,e,f and bicyclic inhibitors 40a-e that exhibited low micromolar activity against a variety of cysteinyl proteinases. 相似文献
54.
Brockhausen I Benn M Bhat S Marone S Riley JG Montoya-Peleaz P Vlahakis JZ Paulsen H Schutzbach JS Szarek WA 《Glycoconjugate journal》2006,23(7-8):525-541
Galactosyltransferases are important enzymes for the extension of the glycan chains of glycoproteins and glycolipids, and
play critical roles in cell surface functions and in the immune system. In this work, the acceptor specificity and several
inhibitors of bovine β1,4-Gal-transferase T1 (β4GalT, EC 2.4.1.90) were studied. Series of analogs of N-acetylglucosamine (GlcNAc) and GlcNAc-carrying glycopeptides were synthesized as acceptor substrates. Modifications were
made at the 3-, 4- and 6-positions of the sugar ring of the acceptor, in the nature of the glycosidic linkage, in the aglycone
moiety and in the 2-acetamido group. The acceptor specificity studies showed that the 4-hydroxyl group of the sugar ring was
essential for β4GalT activity, but that the 3-hydroxyl could be replaced by an electronegative group. Compounds having the
anomeric β-configuration were more active than those having the α-configuration, and O-, S- and C-glycosyl compounds were all active as substrates. The aglycone was a major determinant for the rate of Gal-transfer. Derivatives
containing a 2-naphthyl aglycone were inactive as substrates although quinolinyl groups supported activity. Several compounds
having a bicyclic structure as the aglycone were found to bind to the enzyme and inhibited the transfer of Gal to control
substrates. The best small hydrophobic GlcNAc-analog inhibitor was found to be 1-thio-N-butyrylGlcNβ-(2-naphthyl) with a Ki of 0.01 mM. These studies help to delineate β4GalT–substrate interactions and will aid in the development of biologically
applicable inhibitors of the enzyme. 相似文献
55.
Specific chromosome aberrations in senescent fibroblast cell lines derived from human embryos. 总被引:16,自引:1,他引:16 下载免费PDF全文
P A Benn 《American journal of human genetics》1976,28(5):465-473
In senescent fibroblast cell lines derived from human embryos, the number of chromosome aberrations were found to increase rapidly. In addition to an increase in aneuploidy and polyploidy, a high frequency of dicentrics occurred, but the number of other chromosome abnormalities remained approximately constant. Banding revealed that many of the dicentrics appeared to be end-to-end fusions of whole chromosomes. The involvement of chromosomes was nonrandom. This "telomeric binding" may reflect a progressive decrease in the stability of telomeric sequences or associated enzymes which may also occur in vivo. 相似文献
56.
Supramolecular structures of peptide assemblies in membranes by neutron off-plane scattering: method of analysis 总被引:1,自引:1,他引:1 下载免费PDF全文
In a previous paper (Yang et al., Biophys. J. 75:641-645, 1998), we showed a simple, efficient method of recording the diffraction patterns of supramolecular peptide assemblies in membranes where the samples were prepared in the form of oriented multilayers. Here we develop a method of analysis based on the diffraction theory of two-dimensional liquids. Gramicidin was used as a prototype model because its pore structure in membrane in known. At full hydration, the diffraction patterns of alamethicin and magainin are similar to gramicidin except in the scale of q (the momentum transfer of scattering), clearly indicating that both alamethicin and magainin form pores in membranes but of different sizes. When the hydration of the multilayer samples was decreased while the bilayers were still fluid, the in-plane positions of the membrane pores became correlated from one bilayer to the next. We believe that this is a new manifestation of the hydration force. The effect is most prominent in magainin patterns, which are used to demonstrate the method of analysis. When magainin samples were further dehydrated or cooled, the liquid-like diffraction turned into crystal-like patterns. This discovery points to the possibility of investigating the supramolecular structures with high-order diffraction. 相似文献
57.
58.
59.
Dahia PL Ross KN Wright ME Hayashida CY Santagata S Barontini M Kung AL Sanso G Powers JF Tischler AS Hodin R Heitritter S Moore F Dluhy R Sosa JA Ocal IT Benn DE Marsh DJ Robinson BG Schneider K Garber J Arum SM Korbonits M Grossman A Pigny P Toledo SP Nosé V Li C Stiles CD 《PLoS genetics》2005,1(1):72-80
60.