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181.
Clare BW Scozzafava A Briganti F Iorga B Supuran CT 《Journal of enzyme inhibition》2000,15(3):235-264
Two series of derivatives have been prepared and assayed as inhibitors of two physiologically relevant serine proteases, human thrombin and human trypsin. The first series includes alkyl-/ aralkyl-/aryl- and hetarylsulfonyl-aminoguanidines. It was thus observed that sulfanilyl-aminoguanidine possesses moderate but intrinsically selective thrombin inhibitory properties, with KI values around 90 and 1400 nM against thrombin and trypsin respectively. Further elaboration of this molecule afforded compounds that inhibited thrombin with KI values in the range 10-50 nM, whereas affinity for trypsin remained relatively low. Such compounds were obtained either by attaching benzyloxycarbonyl- or 4-toluenesulfonylureido-protected amino acids (such as D-Phe, L-Pro) or dipeptides (such as Phe-Pro, Gly His, beta-Ala-His or Pro-Gly) to the N-4 atom of the lead molecule, sulfanilyl-aminoguanidine, or by attaching substituted-pyridinium propylcarboxamido moieties to this lead. Thus, this study brings novel insights regarding a novel non-basic S1 anchoring moiety (i.e., SO2NHNHC(=NH)NH2), and new types of peptidomimetic scaffolds obtained by incorporating tosylureido-amino acids/pyridinium-substituted-GABA moieties in the hydrophobic binding site(s). Structure-activity correlations of the new serine protease inhibitors are also discussed based on a QSAR model described previously for a large series of structurally-related derivatives (Supuran et al. (1999) J. Med. Chem., in press). 相似文献
182.
Finlay BB Brumell JH 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2000,355(1397):623-631
Salmonellosis (diseases caused by Salmonella species) have several clinical manifestations, ranging from gastroenteritis (food poisoning) to typhoid (enteric) fever and bacteraemia. Salmonella species (especially Salmonella typhimurium) also represent organisms that can be readily used to investigate the complex interplay that occurs between a pathogen and its host, both in vitro and in vivo. The ease with which S. typhimurium can be cultivated and genetically manipulated, in combination with the availability of tissue culture models and animal models, has made S. typhimurium a desirable organism for such studies. In this review, we focus on Salmonella interactions with its host cells, both in tissue culture (in vitro) and in relevant animal models (in vivo), and compare results obtained using these different models. The recent advent of sophisticated imaging and molecular genetic tools has facilitated studying the events that occur in disease, thereby confirming tissue culture results, yet identifying new questions that need to be addressed in relevant disease settings. 相似文献
183.
Identification of methyl farnesoate in the cypris larva of the barnacle, Balanus amphitrite, and its role as a juvenile hormone 总被引:1,自引:0,他引:1
Smith PA Clare AS Rees HH Prescott MC Wainwright G Thorndyke MC 《Insect biochemistry and molecular biology》2000,30(8-9):885-890
Previous investigations have shown that insect juvenile hormone (JH) and its analogues induce precocious metamorphosis of barnacle cypris larvae. In the present study, methyl farnesoate (MF; structurally identical to JH III, except for the absence of an epoxide group) has been shown to have a concentration-dependent effect on the development of cyprids of the barnacle Balanus amphitrite. Analysis of cypris extracts by gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) confirmed the presence of endogenous MF. These data provide evidence that MF functions as a juvenilizing hormone in barnacle cyprids, an effect that hitherto has not been noted. 相似文献
184.
Jeffrey J. Wine Damjan Glavač Gregory Hurlock Clare Robinson Margaret Lee Uros Potočnik Metka Ravnik-Glavač Michael Dean 《Mammalian genome》1998,9(4):301-305
Cystic fibrosis is a common human genetic disease caused by mutations in CFTR, a gene that codes for a chloride channel that
is regulated by phosphorylation and cytosolic nucleotides. As part of a program to discover natural animal models for human
genetic diseases, we have determined the genomic sequence of CFTR in the Rhesus monkey, Macaca mulatta. The coding region of rhesus CFTR is 98.3% identical to human CFTR at the nucleotide level and 98.2% identical and 99.7% similar at the amino acid level. Partial
sequences of flanking introns (5582 base pair positions analyzed) revealed 91.1% identity with human introns. Relative to
rhesus intronic sequence, the human sequences had 27 insertions and 22 deletions. Primer sequences for amplification of rhesus
genomic CFTR sequences are provided. The accession number is AF013753 (all 27 exons and some flanking intronic sequence).
Received: 27 August 1992 / Accepted: 5 December 1997 相似文献
185.
186.
K Matsumura M Nagano Y Kato-Yoshinaga M Yamazaki A S Clare N Fusetani 《Proceedings. Biological sciences / The Royal Society》1998,265(1408):1825-1830
Immunological investigation has revealed that a settlement-inducing protein complex (SIPC), which induces cypris settlement of the barnacle Balanus amphitrite, is synthesized during larval development and accumulates in the cypris larva. We previously purified the SIPC from adult B. amphitrite, which was active when bound to a substratum. The SIPC is a glycoprotein of high molecular mass, consisting of three major subunits of 76, 88 and 98 kDa with lentil lectin (LCA)-binding sugar chains. In the present study, we prepared antiserum against each LCA-binding subunit of SIPC, and performed immunoblot analyses. Immunoblotting of adult extracts showed that anti-76-kDa antibody reacted only with the 76-kDa protein, whereas anti-88-kDa and anti-98-kDa antibodies reacted with both the 88-kDa and the 98-kDa proteins. Immunoblotting of larval extracts indicated that reactivity of the 76-kDa protein to anti-76-kDa antiserum increased during larval development and cyprid extracts reacted strongly. Moreover, by using immunostaining we found that the SIPC was contained in ''footprints'' of cyprids, which have been shown to act as a settlement-inducing pheromone, and is secreted onto the antennular attachment discs. The results suggest that the SIPC (or SIPC-like proteins) is involved in both adult-larva and larva-larva interactions during settlement of the barnacle B. amphitrite. 相似文献
187.
188.
Eric W. Ainscough Andrew M. Brodie William A. Denny Graeme J. Finlay John D. Ranford 《Journal of inorganic biochemistry》1998,70(3-4):175-185
The preparation of N-, S- and O-donor ligand adducts with CuX+(HX=6-methyl-2-formylpyridinethiosemicarbazone (6HL); 2-formylpyridine-2′-methylthiosemicarbazone (2′L); 2-formylpyridine-4′-methylthiosemicarbazone (4′HL)) is described. The N-donors, 2,2′-bipyridyl (bipy), 4-dimethylaminopyridine (dmap) give the complexes [Cu(6L)(bipy)]PF6, [Cu(6L)(bipy)]Cl·5H2O, [Cu(4′L)(bipy)]PF6, [Cu(6L)(dmap)2]PF6·2.5 H2O and [Cu(4′L)(dmap)2]PF6·H2O which have been characterized by physical and spectroscopic techniques. Pentafluorothiophenolate (pftp) gives S-donor complexes [CuX(pftp)] (X=6L and 4′L) and thiolato co-ordination is proposed on the basis of spectroscopic evidence. Paratritylphenolate (ptp) and HPO2−4 give O-donor complexes [Cu(6L)(ptp)], [Cu(4′L)(ptp)], [{Cu(6L)}2HPO4]·4H2O, and [{Cu(4′L)}2HPO4]·5H2O which have been characterized by physical and spectroscopic techniques, as have the precursor complexes [Cu(6L)(CH3COO)]·H2O, [Cu(4′L)(CH3COO)], Cu(6HL)(CF3COO)](CF3COO)·0.5H2O, [Cu(4′HL)(CF3COO)](CF3COO), [Cu(2′L)Cl2] and [Cu(2′L)(NO3)2]. Protonation constants for the ligands and some of their complexes have been determined. 2-Formylpyridinethiosemicarbazone (HL) complexes of silver, gold, zinc, mercury, cadmium and lead are also discussed. Cytotoxicity against the human tumor cell line HCT-8 and antiviral data for selected compounds are presented. 相似文献
189.
Role of UEV-1, an Inactive Variant of the E2 UbiquitinConjugating Enzymes, in In Vitro Differentiation and Cell Cycle Behavior of HT-29-M6 Intestinal Mucosecretory Cells 总被引:1,自引:0,他引:1 下载免费PDF全文
190.
Zygotene synaptonemal complex karyotyping of five strains of diploid Tradescantia was carried out using the whole mount spreading technique. The presence of pairing partner switches in the zygotene preparations suggested the presence of chromosomal structural heterozygosity. Metaphase and Anaphase I analysis confirmed the presence of heterozygous translocations and inversions. Two plants analyzed had large centric fragments. In a nucleus from one, the fragments were completely synapsed; in a nucleus from the other, there was very little synapsis. Difficulties arose in adapting the whole mount spreading technique to the long Tradescantia chromosomes. Variability was encountered in both the contrast obtained and in the degree to which the chromosomal axes were stretched. Possible sources of the variability are discussed. 相似文献