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排序方式: 共有1018条查询结果,搜索用时 406 毫秒
1.
Dr. Raysa Khan Tareque Dr. Storm Hassell-Hart Dr. Tobias Krojer Dr. Anthony Bradley Dr. Srikannathasan Velupillai Dr. Romain Talon Dr. Michael Fairhead Dr. Iain J. Day Kamlesh Bala Dr. Robert Felix Dr. Paul D. Kemmitt Prof. Paul Brennan Prof. Frank von Delft Dr. Laura Díaz Sáez Prof. Kilian Huber Prof. John Spencer 《ChemMedChem》2020,15(24):2513-2520
Combined photochemical arylation, “nuisance effect” (SNAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with SNAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified. 相似文献
2.
3.
Dr. Iain J. W. McKean Prof. Paul A. Hoskisson Prof. Glenn A. Burley 《Chembiochem : a European journal of chemical biology》2020,21(20):2890-2897
This Concept article describes the latest developments in the emerging area of late-stage biocatalytic alkylation. Central to these developments is the ability to efficiently prepare S-adenosyl methionine (SAM) cofactor analogues and couple this with enzymatic alkyl transfer. Recent developments in the enzymatic synthesis of SAM cofactor analogues are summarized first, followed by their application as alkyl transfer agents catalyzed by methyltransferases (MTases). Second, innovative methods to regenerate SAM cofactors by enzymatic cascades is reported. Finally, future opportunities towards establishing a generalized platform for late-stage alkylation are described. 相似文献
4.
The authors report a meta-analysis of age differences in everyday problem-solving/decision-making effectiveness (EPSE). Effect sizes were calculated to reflect 3 age group comparisons: old versus young, young versus middle-aged, and middle-aged versus old. Findings from the meta-analysis of 28 separate studies with an aggregate of 4,482 participants do not support theories of preserved EPSE in late adulthood. Although significant age differences of moderate magnitude persisted across methodological and theoretical domains, rating criteria (experimenter vs. participant) emerged as a significant moderator of the effect magnitude and direction. In addition, EPSE in older adults was bolstered when problem content was interpersonal and when samples were highly educated. Finally, the current results support the conceptual integration of findings from the everyday problem-solving and everyday decision-making literatures. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
5.
Present-day computer-aided design (CAD) packages play only a small part in the area of mechanical engineering design, which involves the synthesis and embodiment of physical components to perform a pre-determined function without unwanted side effects. The computer cannot properly help the designer in this task until it is able to capture and process the function requirements of the design. This paper describes the computer system being developed for this purpose at the Engineering Design Centre at Cambridge University Engineering Department. The paper also explores some of the geometrical and programming implications raised. 相似文献
6.
M Jarman HM Coley IR Judson TJ Thornton DE Wilman G Abel CJ Rutty 《Canadian Metallurgical Quarterly》1993,36(26):4195-4200
In exploring the structural features which determine the antitumor activity of 2,4,6-tris-[(hydroxymethyl)methylamino]-1,3,5-triazine (trimelamol, 1), we have synthesized analogues in which the methyl groups have been replaced by the electron-withdrawing substituents 2,2,2-trifluoroethyl (5), propargyl (13), and cyanomethyl (15) via the respective tris(alkylamino)triazines 3, 12, and 14. Three mono[(hydroxymethyl)amino]triazines (4, 7, and 10) were also prepared. All the new tris(hydroxymethyl) derivatives showed cytotoxicities toward a variety of experimental rodent and human ovarian tumor cell lines similar to those shown by 1, the cyanomethyl analogue (15) having the most favorable profile. Mono(hydroxymethyl) derivatives (4 and 7) were ca. one-third as toxic. The new tris(hydroxymethyl) analogues were more stable to aqueous hydrolysis than was 1. Half-life (pH 7.5) values were, for 1, 120 min, for 5, 690 min, for 13, 450 min, and for 15, 275 min, but at pH 2.0, 15 (t1/2 350 min) was the most stable. This cyanomethyl analogue was also the most water-soluble, being comparable to 1 whereas 5 and 13 were poorly soluble. 相似文献
7.
MH Thornton DB Johns JD Campeau F Hoehler GS DiZerega 《Canadian Metallurgical Quarterly》1998,13(6):1480-1485
The objective of this study was to assess the safety and to make a preliminary assessment of the efficacy of 0.5% ferric hyaluronate adhesion prevention gel in reducing adhesions in patients undergoing peritoneal cavity surgery by laparotomy, with a planned 'second-look' laparoscopy. The study was a randomized, open-label, placebo-controlled, parallel-group design in patients desirous of fertility at the Women's and Children's Hospital, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California. Female patients aged 24 to 41 years received 300 ml 0.5% ferric hyaluronate adhesion prevention gel or lactated Ringer's solution as an intraperitoneal instillate at the completion of the laparotomy procedure. At second-look laparoscopy 4-12 weeks after the laparotomy, the presence of adhesions was evaluated. Haematology and serum chemistry were determined throughout the study interval. All patients tolerated the procedures well and did not manifest any serious adverse events. At second-look laparoscopy, patients treated with 0.5% ferric hyaluronate adhesion prevention gel had significantly fewer adhesions than control patients. When adhesions did form, they were significantly less extensive and less severe in patients who received 0.5% ferric hyaluronate adhesion prevention gel. In conclusion, 0.5% ferric hyaluronate adhesion prevention gel was safe and highly efficacious in the reduction of the number, severity and extent of adhesions throughout the entire abdomen following peritoneal cavity surgery. 相似文献
8.
JH Viles JB Mitchell SL Gough PM Doyle CJ Harris PJ Sadler JM Thornton 《Canadian Metallurgical Quarterly》1996,242(2):352-362
The aqueous solution structure of the cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-) has been determined by two-dimensional 1H-NMR spectroscopy, combined with a conformational search and distance-geometry calculations. As many as five conformers in slow exchange were observed, and the rate of interconversion between components was measured from the build-up rates of exchange peaks. NMR data allowed the structures of the two predominant conformers to be determined. The major component (66%) contained a cis-proline as part of a type-VIa2 beta-turn encompassing residues Asp-Val-cis-Pro-Ser. The second component (16%) contained only trans-amide bonds, and a type-VIII beta-turn formed by residues Val-Pro-Ser-D-Leu. These structures are discussed in relation to the (phi, psi), space available to the cyclic pentapeptide, determined by a conformational search, and in relation to previously published cyclic-pentapeptide structures. The molecule exhibits activity in a scintillation-proximity assay for the inhibition of the interaction between the integrin very-late antigen-4 (VLA-4; alpha 4 beta 1) and vascular-cell-adhesion molecule-1 (VCAM-1). The structure/activity relationship of the LDV sequence is discussed and related to the recently published X-ray structure of VCAM-1. The relevance of the work to the design of anti-inflammatory drugs is discussed. 相似文献
9.
RM Bionta G Blewitt CB Bratton D Casper A Ciocio R Claus M Crouch ST Dye S Errede GW Foster W Gajewski KS Ganezer M Goldhaber TJ Haines TW Jones D Kielczewska WR Kropp JG Learned JM LoSecco J Matthews HS Park LR Price F Reines J Schulz S Seidel E Shumard D Sinclair HW Sobel JL Stone L Sulak R Svoboda G Thornton van der Velde JC C Wuest 《Canadian Metallurgical Quarterly》1987,36(1):30-36
10.
In this study, we examine the effects of binding to protein upon nucleotide conformation, by the comparison of X-ray crystal structures of free and protein-bound nucleotides. A dataset of structurally non-homologous protein-nucleotide complexes was derived from the Brookhaven Protein Data Bank by a novel protocol of dual sequential and structural alignments, and a dataset of native nucleotide structures was obtained from the Cambridge Structural Database. The nucleotide torsion angles and sugar puckers, which describe nucleotide conformation, were analysed in both datasets and compared. Differences between them are described and discussed. Overall, the nucleotides were found to bind in low energy conformations, not significantly different from their 'free' conformations except that they adopted an extended conformation in preference to the 'closed' structure predominantly observed by free nucleotide. The archetypal conformation of a protein-bound nucleotide is derived from these observations. 相似文献