A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride. Alternative syntheses employing hydrogenation methods have also been developed. These new 9-N-alkyl derivatives possess excellent antimicrobial activity in vitro and in vivo, especially when administered orally to treat experimental infections in mice. From structure-activity studies, 9-N-(1-propyl)erythromycylamine (LY281389) was selected as the most efficacious derivative. These methods have also been extended to the synthesis of some 9-N,N-dialkyl derivatives of erythromycylamine. 相似文献
The kinetics of endogenous protein phosphorylation and resultant phosphoprotein patterns were investigated in well-differentiated (DMTC) and undifferentiated (AMTC) medullary thyroid carcinomas of the rat. Cytosolic or particulate fractions from these tumors were incubated with gamma-32P-ATP in the presence of various effectors. Phosphorylation appeared to be predominantly independent of exogenously added cyclic AMP. Magnesium and manganese were equally effective cofactors. For both tumor types 32P incorporation into cytosolic proteins was maximal within 3-4 min after addition of ATP and subsequently decreased gradually within 1 h. In contrast, in particulate preparations maximal incorporation was reached within 30 s and remained constant over a relatively long time span. In both cases, however, 32P incorporation in extracts from DMTCs were 50-100% higher as compared to AMTCs. Comparison of the phosphoprotein patterns of each tumor after in vitro phosphorylation showed some significant differences. A phosphoprotein with molecular weight of 90 kilodalton (90 kD) was exclusively expressed in the cytosol of DMTC, whereas 99- and 84-kD phosphoproteins were only present in the cytosol of AMTC. The DMTC particulate fraction contained two phosphoproteins (with molecular weights of 40 and 37 kD), which were absent from that of AMTC. In addition, a number of proteins were more intensely phosphorylated in one of the tumors, e.g. proteins of 94 and 33 kD in DMTC cytosol and a protein of 78 kD in AMTC cytosol. Calcium induced phosphorylation of five proteins in DMTC cytosol (with molecular weights of 69, 55, 49, 43 and 32 kD), which were less intensely or not phosphorylated in AMTC. Tyrosine kinase activity was investigated using exogenously added poly(glutamine:tyrosine, 4:1) as an artificial substrate. Cytosolic tyrosine kinase activity in DMTC was +/- 50% higher than in AMTC (11.9 +/- 0.6 and 8.2 +/- 1.7 pmol/mg/min, respectively). The enzyme activities in the particulate preparations were much higher than in the cytosols (+/- 100 pmol/mg/min), although considerable variations in enzyme activity between different tumors of either type were observed. Quantitative differences in tyrosine kinase activity between AMTC and DMTC particulate fractions did not seem to exist using this substrate. Phosphoamino acid analysis of endogenously phosphorylated proteins in both AMTC and DMTC showed phosphotyrosine to be present only in cytosolic proteins within the 50-kD molecular weight region, the majority of 32P being on serine and some on threonine.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
A series of 20-deoxo-20-cyclic (alkylamino) derivatives of tylosin, desmycosin, macrocin and lactenocin was prepared by reductive amination of the C-20 aldehyde group. The majority of the compounds were prepared using metal hydrides (sodium cyanoborohydride or sodium borohydride) as the reducing agents and a suitable cyclic alkylamine. Subsequently, a more convenient procedure was developed using formic acid as a reducing agent. The C-20 amino derivatives prepared from desmycosin exhibited good in vitro antimicrobial activity against Pasteurella haemolytica and Pasteurella multocida (MIC range of 0.78 approximately 6.25 micrograms/ml) as well as Mycoplasma species (MIC range of 0.39 approximately 6.25 micrograms/ml). Several derivatives showed excellent oral efficacy against infections caused by P. multocida in chicks. One of these derivatives, 20-deoxo-20-(3,5-dimethylpiperidin-1-yl)desmycosin (tilmicosin or EL-870) was selected for development as a therapeutic agent for pasteurellosis in calves and pigs. 相似文献
A second-generation 5000 rad radiation hybrid (RH) map of the cattle genome was constructed primarily using cattle ESTs that were targeted to gaps in the existing cattle-human comparative map, as well as to sparsely populated map intervals. A total of 870 targeted markers were added, bringing the number of markers mapped on the RH(5000) panel to 1913. Of these, 1463 have significant BLASTN hits (E < e(-5)) against the human genome sequence. A cattle-human comparative map was created using human genome sequence coordinates of the paired orthologs. One-hundred and ninety-five conserved segments (defined by two or more genes) were identified between the cattle and human genomes, of which 31 are newly discovered and 34 were extended singletons on the first-generation map. The new map represents an improvement of 20% genome-wide comparative coverage compared with the first-generation map. Analysis of gene content within human genome regions where there are gaps in the comparative map revealed gaps with both significantly greater and significantly lower gene content. The new, more detailed cattle-human comparative map provides an improved resource for the analysis of mammalian chromosome evolution, the identification of candidate genes for economically important traits, and for proper alignment of sequence contigs on cattle chromosomes. 相似文献
Summary: The complex dynamics of poly(n‐alkyl methacrylates) is studied by advanced 13C NMR spectroscopy as well as mechanical and dielectric relaxation. Extended backbone conformations are identified as the molecular units involved in structural relaxation. From the variation in the degree of polymerization and a comparison with the presence of stereoregular sequences in the sample, the length of the extended units is determined to involve about five, at most ten monomeric units. Syndiotactic and isotactic sequences behave similarly. These findings are indicative of locally structured polymer melts.
Summary Cephalic pancreatoduodenectomy (CPD) with pylorus preservation has been suggested to improve the functional and nutritional result of surgery. At operation, the first two centimeters of the duodenum are preserved, the vascular arch of the lesser gastric curvature is saved and the right gastroepiploic artery is resected at its origin. The aim of this study on 15 fresh cadavers was to determine the origin of the vascularization of the remaining duodenum and also the possibilities of preserving an optimal vascularization after CPD and pylorus preservation. All of the arteries supplying the remaining duodenum and arising either from the right gastric artery or the right gastroepiploic artery were identified. The distances between the origin of the infrapyloric artery and the termination of the gastroduodenal artery on the cranial and ventral pancreaticoduodenal artery and the left gastroepiploic artery were measured. At CPD with pylorus preservation, the study demonstrated that: 1) the cranial side of the remaining duodenum remains vascularized in 80% of the cases by one or two supraduodenal branches coming from the right gastric artery; 2) ligation of the right gastroepiploic artery eliminates all vascular supply to the caudal side of the remaining duodenum in almost half of the cases; 3) in these cases, the dissection of the bifurcation of the gastroduodenal artery and the vascular section beyond the origin of the infrapyloric artery allowed a direct vascular supply to the remaining duodenum to be preserved.This work was presented at the French Section of the European Association of Clinical Anatomy meeting, Bobigny, France, 1992 相似文献