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61.
62.
Jarkko Rautio Jukka Leppänen Marko Lehtonen Krista Laine Mikko Koskinen Jarmo Pystynen Jouko Savolainen Mikko Sairanen 《Bioorganic & medicinal chemistry letters》2010,20(8):2614-2616
Compound 1 is an investigational, nanomolar inhibitor of catechol-O-methyltransferase (COMT) that suffers from poor oral bioavailability, most probably due to its low lipophilicity throughout most of the gastrointestinal tract and, to a lesser extent, its rapid systemic clearance. Several lipophilic esters were designed as prodrugs and synthesized in an attempt to optimize presystemic drug absorption. A modest twofold increase in 6-h exposure of 1 was observed with two prodrugs, compared to that of 1, after oral treatment in rats. 相似文献
63.
Chiao-Feng Lin Stephen M Mount Artur Jarmołowski Wojciech Makałowski 《BMC evolutionary biology》2010,10(1):47
Background
Many multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors. The major (U2) spliceosome processes the vast majority of introns, referred to as U2-type introns, while the minor (U12) spliceosome removes a small fraction (less than 0.5%) of introns, referred to as U12-type introns. U12-type introns have distinct sequence elements and usually occur together in genes with U2-type introns. A phylogenetic distribution of U12-type introns shows that the minor splicing pathway appeared very early in eukaryotic evolution and has been lost repeatedly. 相似文献64.
Xing L Huhtala M Pietiäinen V Käpylä J Vuorinen K Marjomäki V Heino J Johnson MS Hyypiä T Cheng RH 《The Journal of biological chemistry》2004,279(12):11632-11638
Integrins are cell surface receptors for several microbial pathogens including echovirus 1 (EV1), a picornavirus. Cryo-electron microscopy revealed that the functional domain (alpha(2)I) of human alpha(2)beta(1) integrin binds to a surface depression on the EV1 capsid. This three-dimensional structure of EV1 bound to alpha(2)I domain provides the first structural details of an integrin interacting with a picornavirus. The model indicates that alpha(2)beta(1) integrin cannot simultaneously bind both EV1 and the physiological ligand collagen. Compared with collagen binding to the alpha(2)I domain, the virus binds with a 10-fold higher affinity but in vitro uncoating of EV1 was not observed as a result of attachment of alpha(2)I. A molecular model, constructed on the basis of the EV1-integrin complex, shows that multiple alpha(2)beta(1) heterodimers can bind at adjacent sites around the virus 5-fold symmetry axes without steric hindrance. In agreement with this, virus attachment to alpha(2)beta(1) integrin on the cell surface was found to result in integrin clustering, which can give rise to signaling and facilitate the initiation of the viral entry process that takes place via caveolae-mediated endocytosis. 相似文献
65.
66.
Jansson A Niemi J Lindqvist Y Mäntsälä P Schneider G 《Journal of molecular biology》2003,334(2):269-280
Anthracyclines are aromatic polyketide antibiotics, and several of these compounds are widely used as anti-tumor drugs in chemotherapy. Aclacinomycin-10-hydroxylase (RdmB) is one of the tailoring enzymes that modify the polyketide backbone in the biosynthesis of these metabolites. RdmB, a S-adenosyl-L-methionine-dependent methyltransferase homolog, catalyses the hydroxylation of 15-demethoxy-epsilon-rhodomycin to beta-rhodomycin, one step in rhodomycin biosynthesis in Streptomyces purpurascens. The crystal structure of RdmB, determined by multiwavelength anomalous diffraction to 2.1A resolution, reveals that the enzyme subunit has a fold similar to methyltransferases and binds S-adenosyl-L-methionine. The N-terminal domain, which consists almost exclusively of alpha-helices, is involved in dimerization. The C-terminal domain contains a typical alpha/beta nucleotide-binding fold, which binds S-adenosyl-L-methionine, and several of the residues interacting with the cofactor are conserved in O-methyltransferases. Adjacent to the S-adenosyl-L-methionine molecule there is a large cleft extending to the enzyme surface of sufficient size to bind the substrate. Analysis of the putative substrate-binding pocket suggests that there is no enzymatic group in proximity of the substrate 15-demethoxy-epsilon-rhodomycin, which could assist in proton abstraction and thus facilitate methyl transfer. The lack of a suitably positioned catalytic base might thus be one of the features responsible for the inability of the enzyme to act as a methyltransferase. 相似文献
67.
68.
Several years ago it was discovered that plant transformation with a transcribed sense transgene could shut down the expression of a homologous endogenous gene. Moreover, it was shown that the introduction into the cell of dsRNA (double-stranded RNA) containing nucleotide sequence complementary to an mRNA sequence causes selective degradation of the latter and thus silencing of a specific gene. This phenomenon, called RNA interference (RNAi) was demonstrated to be present in almost all eukaryotic organisms. RNAi is also capable of silencing transposons in germ line cells and fighting RNA virus infection. Enzymes involved in this process exhibit high homology across species. Some of these enzymes are involved in other cellular processes, for instance developmental timing, suggesting strong interconnections between RNAi and other metabolic pathways. RNAi is probably an ancient mechanism that evolved to protect eukaryotic cells against invasive forms of nucleic acids. 相似文献
69.
Orr S Alexandre E Clark B Combes R Fels LM Gray N Jönsson-Rylander AC Helin H Koistinen J Oinonen T Richert L Ravid R Salonen J Teesalu T Thasler W Trafford J Van Der Valk J Von Versen R Weiss T Womack C Ylikomi T 《Cell and tissue banking》2002,3(2):133-137
This is a report of a workshop held on the establishment of human research tissue banking which was held in Levi, Finland
21–24 March 2002.There were 21 participants from 7 European countries. This meeting was attended by representatives from academia,
research tissue banks and from the Biotech and Pharmaceutical Industries. The principal aim of the workshop was to find a
way to progress the recommendations from ECVAM workshop 44 (ATLA 29, 125–134,2001) and ECVAM workshop 32 (ATLA 26, 763–777,
1998). The workshop represented the first unofficial meeting of the European Network of Research Tissue Banks (ENRTB) steering
group. It is expected that in the period preceding the next workshop the ENRTB steering group will co-ordinate the ethical,legislative
and organisational aspects of research tissue banking. Key issues dealt with by the Levi workshop included the practical aspects
of sharing expertise and experiences across the different European members. Such collaboration between research tissue banks
and end users of such material seeks to ultimately enable shared access to human tissue for medical and pharmaco-toxicological
research while maintaining strict adherence to differences in legal and ethical aspects related to the use of human tissue
in individual countries.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
70.
Pirjo Kainulainen† Anne Nissinen† Anne Piirainen‡ Kari Tiilikkala† Jarmo K. Holopainen† 《Agricultural and Forest Entomology》2002,4(3):211-216
- 1 The carrot psyllid Trioza apicalis and Lygus rugulipennis can cause serious damage to cultivated carrots, especially at the seedling stage. The essential oil composition in leaves of several carrot varieties was studied in relation to oviposition acceptance by sucking insect herbivores that have different feeding strategies. Of the insect species studied, T. apicalis is a carrot specialist, T. anthrisci is an Apiaceae specialist, and L. rugulipennis is a generalist.
- 2 The oil composition differed significantly between leaves from different carrot varieties (Flakkeer 2, Nantura, Parano, Napoli, Panther, Splendid, Nantes 3 Express).
- 3 There were no differences in the mean numbers of eggs laid by T. apicalis or T. anthrisci on different varieties, but L. rugulipennis laid fewer eggs on the Panther variety than on Nantes 3 Express.
- 4 There was a negative linear correlation between limonene concentration and number of eggs laid by T. apicalis, confirming that limonene is a repellent to the carrot psyllid. Results suggest that only particular compounds influence the preference of the carrot psyllid, and these compounds may not be the main components in the essential oil of carrots.
- 5 A positive correlation was found between myrcene concentration and number of eggs laid by T. anthrisci. Essential oil composition did not explain egg‐laying preference of L. rugulipennis.
- 6 The results indicate that essential oil composition of carrot varieties affects host preference of Apiaceae specialists more than that of generalists.