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Jeffery B. Press James J. McNally Pauline J. Sanfilippo Michael F. Addo Deborah Loughney Edward Giardino Laurence B. Katz Robert Falotico Barbara J. Haertlein 《Bioorganic & medicinal chemistry》1993,1(6):423-435
The syntheses and antihypertensive activity of the thieno[3,4-b]pyran and thieno[2,3-b]pyran isosteres of the potassium channel opener (PCO) RWJ 26629 (± 2a) are reported. While the unsubstituted thiophene derivatives were active at 20 mg/kg, introduction of a strong electron withdrawing group in the 2-position of the thieno[3,2-b] series increased potency. Similar substitution on the thieno[3,4-b] series significantly lowered potency. Compounds 26 and 30 are approximately 5-fold more potent than the prototypic PCO cromakalim (± 1). 相似文献
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Nicholas J. Talbot Pauline Vincent Howard G. Wildman 《Fungal genetics and biology : FG & B》1996,20(4):254-267
Talbot, N. J., Vincent, P., and Wildman, H. G. 1996. The influence of genotype and environment on the physiological and metabolic diversity ofFusarium compactum. Fungal Genetics and Biology20,254–267. Fungal species produce a large variety of secondary metabolites which are of considerable interest to the pharmaceutical industry. It is clear that the secondary metabolite production of a species varies significantly in strains from different geographic locations and from different habitats. The influence of genotype and environment on metabolite production is, however, poorly understood. In this study we examined the influence of genotypic variability, physiological variability, environmental location, and habitat on metabolite production byFusarium compactum.Isolates of the fungus from two geographic locations and two distinct habitat types were examined for growth on 95 different carbon sources, and genotypic variability was determined using RAPDs and rDNA–RFLP analysis. In a blind test secondary metabolite production was assessed using HPLC profiles of methanolic cell extracts. A number of correlations were observed between genotypic groupings, as determined using parsimony, and specific metabolite production. Similar correlations were also observed with physiological groups although genotypic analysis proved to be a more sensitive predictor of metabolite variability. The data suggest a complex relationship between environment, genotype, and metabolite production but highlight the use of genetic screening as a means of optimizing the chances of identifying a wide range of metabolites from a given species. 相似文献
25.
Esther Van de Vosse Paola Van der Bent Joris J. Heus Gert- Jan B. Van Ommen Johan T. Den Dunnen 《Mammalian genome》1997,8(7):497-501
The disease loci for X-linked Retinoschisis (RS), Keratosis follicularis spinulosa decalvans (KFSD), and Coffin-Lowry syndrome
(CLS) have been localized to the same, small region in Xp22 on the human X Chromosome (Chr). To generate a high-resolution
map of the available contig in this area, we have used the YAC fragmentation vectors pBP108/ADE2 and pBP109/ADE2 and generated fragmented YACs from a 2.5-Mb YAC (y939H7) spanning the mentioned disease gene candidate regions. Forty-seven
fragmented YACs were generated and analyzed, ranging in size from 170 kb to over 2400 kb. The resulting YAC fragmentation
panel was used to construct a detailed restriction map of the region and has been used to bin clones and markers. As a deletion
panel, it will present a valuable resource for further mapping.
Received: 31 December 1996 / Accepted: 22 February 1997 相似文献
26.
Data on cyanobacteria (blue-green algae) are generallycollected on a reactive basis, frequently in responseto bloom events. Such data presents a biased andincomplete snapshot of water quality. This paper looksat two typical data sets for UK waters showing thatwhile statistics may be used to describe the data theyare of limited use in forecasting. Suggestions ofappropriate tests for small and sparse data sets aremade. 相似文献
27.
S. S. Wijmenga H. A. Heus H. A. E. Leeuw H. Hoppe M. van der Graaf C. W. Hilbers 《Journal of biomolecular NMR》1995,5(1):82-86
Summary A new 1H−13C−31P triple resonance experiment is described which allows unambigous sequential backbone assignment in 13C-labeled oligonucleotides via through-bond coherence transfer from 31P via 13C to 1H. The approach employs INEPT to transfer coherence from 31P to 13C and homonuclear TOCSY to transfer the 13C coherence through the ribose ring, followed by 13C to 1H J-cross-polarisation. The efficiencies of the various possible transfer pathways are discussed. The most efficient route
involves transfer of 31Pi coherence via C4′i and C4′i-1, because of the relatively large J′PC4 couplings involved. Via the homonuclear and heteronuclear mixing periods, the C4′i and C4′i-1 coherences are subsequently transferred to, amongst others, H1′i and H1′i-1, respectively, leading to a 2D 1H−31P spectrum which allows a sequential assignment in the 31P−1H1′ region of the spectrum, i.e. in the region where the proton resonances overlap least. The experiment is demonstrated on
a 13C-labeled RNA hairpin with the sequence 5′(GGGC-CAAA-GCCU)3′. 相似文献
28.
A computer program and accompanying data matrix have been prepared for bacteria of medical interest, to assist the assignment of an unidentified bacterium to the most likely genus. The results on a set of relatively simple tests are entered. The program prints the more likely genera, followed by a list of diagnostic tables in Cowan & Steel (1974) and Buchanan & Gibbons (1974). Where available, identification matrices for further computer-assisted study, are presented. This program may be of particular help in laboratories where a wide range of bacteria have to be identified. 相似文献
29.
The reduction of ferricytochrome c in the presence of 6-hydroxydopamine/O2 mixtures was examined under various reaction conditions. As the autoxidation of 6-hydroxy-dopamine progressed to completion, there were fluctuations in the net redox reactivity between reducing and oxidizing steady states. This was reflected in a sequence of damped oscillations in the redox state of cytochrome c. Corresponding to the time when 6-hydroxydopamine was 75–100% exhausted, reoxidation of the ferrocytochrome c occurred (prevented by catalase or catalase plus Superoxide dismutase). After the H2O2, in turn, was mostly consumed, the next phase commenced in which the cytochrome c became reduced for a second time. This reductive phase was 52% inhibited by superoxide dismutase. In the subsequent and final phase of the process, a progressive oxidation of cytochrome c lasting at least 24 h was observed. Of the initial reduction of ferricytochrome c, at most 37% can be attributed to direct reduction by 6-hydroxydopamine or its semiquinone. This initial net reduction of cytochrome c was inhibited 51% by superoxide dismutase and 41% by catalase. However, since either catalase or superoxide dismutase inhibited the autoxidation of 6-hydroxydopamine by at least as much as it slowed the reduction of cytochrome c, their effects in slowing the reduction of cytochrome c resulted largely from the decreased production of those free radicals which reduce ferricytochrome c, and only in part from accelerated removal. Elimination of the actions of transition metal ions (whether by passage of the buffer solutions through Chelex 100 resins or by addition of desferrioxamine to the reaction medium) slowed both the reoxidation and rereduction by up to 96%. Addition of mannitol decreased the rate of the first reoxidation by 25% and increased the rate of the rereduction by 7%. In general, the oscillations are explicable in terms of changes in the steady state levels of O2 and H2O2, with metal ions playing a major role and hydroxyl radicals a minor role in both the reoxidation and rereduction. 相似文献
30.
Summary The ultrastructure of the nerves forming the submucous plexus of cervical and thoracic parts of the trachea was studied in the guinea-pig. Specimens were obtained from 6 animals perfused with warm fixative and from 6 animals in which pieces of trachea were incubated in buffer containing 5-hydroxydopamine before being immersed in cold fixative. Of the two types of axonal terminal identified in the nerves, one contained mainly large dense-cored vesicles, and the second contained numerous small vesicles. In specimens incubated in 5-hydroxydopamine, the small vesicles of the latter terminals exhibited the electron-dense cores which are characteristic of adrenergic axonal terminals. Counts made on perfused specimens showed that, in both the thoracic and cervical parts of the trachea, the density of adrenergic terminals was higher than that of terminals containing mainly large dense-cored vesicles. Overall terminal density was, however, higher in the thoracic than in the cervical part of the trachea, and estimates of nerve size showed that this was associated with the presence in the thoracic plexus of a substantially greater proportion of nerves with less than 6 axons. The possible function of the nerves in the control of the calibre of the submucous blood vessels was discussed. 相似文献