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21.
Bortoletto D Goldberg M Horwitz N Mestayer MD Moneti GC Sharma V Shipsey IP Skwarnicki T Csorna SE Letson T Brock IC Ferguson T Artuso M Bebek C Berkelman K Blucher E Byrd J Cassel DG Cheu E Coffman DM Crawford G DeSalvo R DeWire JW Drell PS Ehrlich R Galik RS Gittelman B Gray SW Halling AM Hartill DL Heltsley BK Kandaswamy J Kowalewski R Kreinick DL Kubota Y Lewis JD Mistry NB Mueller J Namjoshi R Nandi S Nordberg E O'Grady C Peterson D Pisharody M Riley D Sapper M Silverman A Stone S Worden H 《Physical review letters》1989,62(21):2436-2439
22.
Alam MS Katayama N Kim IJ Li WC Lou XC Sun CR Bortoletto D Goldberg M Horwitz N Mestayer MD Moneti GC Sharma V Shipsey IP Skwarnicki T Csorna SE Letson T Brock IC Ferguson T Artuso M Bebek C Berkelman K Blucher E Byrd J Cassel DG Cheu E Coffman DM Crawford G DeSalvo R DeWire JW Drell PS Ehrlich R Galik RS Gittelman B Gray SW Halling AM Hartill DL Heltsley BK Kandaswamy J Kowalewski R Kreinick DL Kubota Y Lewis JD Mistry NB Mueller J Namjoshi R Nandi S Nordberg E O'Grady C Peterson D Pisharody M 《Physical review D: Particles and fields》1989,40(11):3790
23.
Silvio De Bernardini Georg Graf Colin A. Leach Peter Bühlmayer Felix Waldmeier Christoph Tamm 《Helvetica chimica acta》1983,66(2):639-651
The modified nucleoside Πd (1) was used in the synthesis of the oligonucleotide d (TpTpΠpCpGpTpCpApApApApTpC). Diester methodology being unsatisfactory, the triester synthesis was investigated with the unnatural nucleoside. An improved method of nucleoside phosphorylation was developed for the synthesis of the fully-protected nucleotide 2e. This molecule could be cleanly and selectively deprotected, and allowed the efficient synthesis of the desired oligonucleotide. 相似文献
24.
Jonathan S. Dordick K. C. Backman R. Balakrishnan R. Brent M. S. Ptashne L. P. Casson S. A. Goff A. L. Goldberg P. A. Cornelius R. M. Hochstrasser N. R. Kallenbach H. Rubin G. J. Todaro H. A. De Boer J. C. Delgoffe M. Lobmann N. ZyGraich L. Gehrke T. Kunkel A. Paau S. G. Platt L. Sequeira M. A. Palladino H. G. Roman D. Hultmark T. T. Rasmusan H. Steiner 《Applied biochemistry and biotechnology》1990,26(1):107-113
Protein engineering and site-directed mutagenesis is becoming immensely important in both fundamental studies and commercial applications involving proteins and enzymes in biocatalysis. Protein engineering has become a powerful tool to help biochemists and molecular enzymologists elucidate structure-function relationships in enzymic active sites, to understand the intricacies of protein folding and denaturation, and to alter the selectivity of enzymatic catalysis. Commercial applications of engineered enzymes are being developed to increase protein stability, widen or narrow substrate specificity, and to develop novel approaches for use of enzymes in organic synthesis, drug design, and clinical applications. In addition to protein engineering, novel expression systems have been designed to prepare large quantities of genetically engineered proteins. Recent US patents and scientific literature on protein engineering, site-directed mutagenesis, and protein expression systems related to protein engineering are surveyed. Patent abstracts are summarized individually and a list of literature references are given. 相似文献
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26.
[reaction: see text] Following the discovery that meso-substituted corroles are formed in solvent-free condensation of pyrrole with aldehydes, we demonstrate that a small variation in the methodology is suitable for facile synthesis of cobalt(III) corrole and hexaphyrin. These compounds, as well as three noncyclic products, were fully characterized by spectroscopy and X-ray crystallography. 相似文献
27.
Arie L. Gutman Marina Etinger Gennady Nisnevich Felix Polyak 《Tetrahedron: Asymmetry》1998,9(24):1022
The enantiomerically pure chiral benzocyclic amines 6–8 were obtained by asymmetric transamination of the corresponding prochiral ketones 9a–c. The method involves: (a) formation of chiral imines 10a–c from the prochiral ketones 9a–c and the inexpensive chiral auxiliary (R)- or (S)-phenylethylamine (PEA); (b) asymmetrically induced reduction of these imines to the diastereomeric amines 11a–c and 12a–c; (c) catalytic hydrogenation to remove the benzylic fragment of the chiral PEA auxiliary. The stereoselectivity of the imine reduction, as well as the regioselectivity of the catalytic hydrogenation, are strongly dependent on the size of the saturated ring condensed with the benzene ring. This approach was used to develop a convenient, high yielding, and stereoselective route to several practically important optically active α-amino substituted benzocyclic compounds. 相似文献
28.
29.
Zepeck F Gräwert T Kaiser J Schramek N Eisenreich W Bacher A Rohdich F 《The Journal of organic chemistry》2005,70(23):9168-9174
[Structure: see text]. The IspG protein is known to catalyze the transformation of 2-C-methyl-d-erythritol 2,4-cyclodiphosphate into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate in the nonmevalonate pathway of isoprenoid biosynthesis. We have found that the apparent IspG activity in the cell extracts of recombinant Escherichia coli cells as observed by a radiochemical assay can be enhanced severalfold by coexpression of the isc operon which is involved in the assembly of iron-sulfur clusters. The recombinant protein was isolated by affinity chromatography under anaerobic conditions. With a mixture of flavodoxin, flavodoxin reductase, and NADPH as the reducing agent, stringent assay methods based on photometry or on 13C NMR detection of multiply 13C-labeled substrate/product ratios afforded catalytic activities greater than 60 nmol mg(-1) min(-1) for the protein "as isolated" (i.e., without reconstitution of any kind). Lower apparent activities were found using photoreduced deazaflavin as an artifactual electron donor, whereas dithionite was unable to serve as an artificial electron donor. The apparent Michaelis constant for 2-C-methyl-D-erythritol 2,4-cyclodiphosphate was 700 microM. The enzyme was inactivated by EDTA and could be reactivated by Mn2+. The pH optimum was at 9.0. The protein contained 2.4 iron ions and 4.4 sulfide ions per subunit. The replacement of any of the three conserved cysteine residues afforded mutant proteins which were devoid of catalytic activity and contained less than 6% of Fe2+ and less than 23% of S2- as compared to the wild-type protein. Sequence comparison indicates that putative IspG proteins of plants, the apicomplexan protozoan Plasmodium falciparum, and bacteria from the Bacteroidetes/Chlorobi group contain an insert of about 170-320 amino acid residues as compared with eubacterial enzymes. 相似文献
30.
Elaine C. Petronilho Murilo M. Pedrote Mayra A. Marques Yulli M. Passos Michelle F. Mota Benjamin Jakobus Gileno dos Santos de Sousa Filipe Pereira da Costa Adriani L. Felix Giulia D. S. Ferretti Fernando P. Almeida Yraima Cordeiro Tuane C. R. G. Vieira Guilherme A. P. de Oliveira Jerson L. Silva 《Chemical science》2021,12(21):7334
Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). The mechanism of the formation of the aggregates in the nucleus remains uncertain. The present study demonstrated that the DNA-binding domain of p53 (p53C) underwent phase separation (PS) on the pathway to aggregation under various conditions. p53C phase separated in the presence of the crowding agent polyethylene glycol (PEG). Similarly, mutant p53C (M237I and R249S) underwent PS; however, the process evolved to a solid-like phase transition faster than that in the case of wild-type p53C. The data obtained by microscopy of live cells indicated that transfection of mutant full-length p53 into the cells tended to result in PS and phase transition (PT) in the nuclear compartments, which are likely the cause of the GoF effects. Fluorescence recovery after photobleaching (FRAP) experiments revealed liquid characteristics of the condensates in the nucleus. Mutant p53 tended to undergo gel- and solid-like phase transitions in the nucleus and in nuclear bodies demonstrated by slow and incomplete recovery of fluorescence after photobleaching. Polyanions, such as heparin and RNA, were able to modulate PS and PT in vitro. Heparin apparently stabilized the condensates in a gel-like state, and RNA apparently induced a solid-like state of the protein even in the absence of PEG. Conditions that destabilize p53C into a molten globule conformation also produced liquid droplets in the absence of crowding. The disordered transactivation domain (TAD) modulated both phase separation and amyloid aggregation. In summary, our data provide mechanistic insight into the formation of p53 condensates and conditions that may result in the formation of aggregated structures, such as mutant amyloid oligomers, in cancer. The pathway of mutant p53 from liquid droplets to gel-like and solid-like (amyloid) species may be a suitable target for anticancer therapy.Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). 相似文献