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微波辅助组合合成的研究进展 总被引:2,自引:0,他引:2
微波辅助组合合成技术是近年来发展起来的一种新的制备化合物库的组合化学技术, 它不仅可以克服传统固相组合合成技术以及液相组合合成技术无法提高产物收率的不足, 而且利用该技术所制得的化合物库中对应的是高纯度的单一化合物, 采用高通量筛选技术可以快速直接地确定高活性结构, 极大地提高了新药开发的效率. 主要就近年来微波辅助组合合成技术的研究进展情况进行介绍, 内容包括固相组合合成、基于聚合物支载的催化剂的组合合成、液相组合合成、氟相组合合成以及组合平行合成等. 相似文献
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动态组合化学是组合化学的一个新兴分支,在药物先导化合物的发现中有广阔的应用前景。在动态组合化学库中,利用靶标分子的诱导结合作用,通过可逆共价反应,能够选择性的筛选到与靶标分子存在强相互作用的优势化合物。本文按照动态组合化学方法简介、动态组合化学中的可逆共价化学、动态组合化学库的分类、动态组合化学库筛选方法的研究进展及动态组合化学在药物先导化合物发现过程中的应用等5个方面对动态组合化学进行了概述。 相似文献
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合理设计一些容量小的、针对特定靶标的化合物库(称为集中库,focused library),是当前组合库设计中的热点。当靶标的三维结构可以通过X射线衍射或NMR等手段确定后,人们就能采用几种不同的策略来进行组合库的设计。本文讨论了在靶标结合位点的约束下,进行组合库设计的主要方法及程序,同时强调了它们的优点与不足。通过这些方法的成功应用实例,显示了它们在新药创制中的广泛应用前景。 相似文献
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催化不对称反应最新进展(Ⅱ)-组合化学方法之 应用 总被引:3,自引:0,他引:3
组合化学技术已经成为药物、新型固体材料和催化剂合成、评价和筛选的一种有力工具,最近它在催化不对称反应的手性催化剂高效率合成与筛选方面的应用也受到了重视,本文将综述组合化学技术在发展不对称合成新型催化剂方面的应用。第一部分主要介绍手性催化剂(或配体)库的固相平行合成;第二部分重点总结了所建立的手性催化剂库的高效率评价技术及其应用。 相似文献
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吸附量热技术和多相催化微观动力学 总被引:2,自引:0,他引:2
本文介绍了多相催化研究中的吸附量热技术、多相催化微观动力学及其计算机模拟, 以及吸附量热技术在定量表征固体催化剂表面中心和在多相催化微观动力学分析中的重要作用。 相似文献
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ZHOU Xiao-Ping 《高等学校化学学报》2000,21(Z1):243
In recent few years combinatorial methodology has been extensively used in material science research. Based on the desired properties of materials, various high throughput synthesizing and screening technologies were developed. These high throughput technologies can increase our speed to more than hundred folds for finding and optimizing materials. One of the most active areas is catalysis. Scientists are developing novel high throughput technologies to screen catalyst libraries to find and optimize new catalysts for chemical industry. In this area die key is combinatorial catalytic reactor design, catalyst library synthesis, and product detection. Systematic technologies for catalyst library synthesis and characterization were developed in our laboratory. In this work, catalyst in situ synthesis, parallel reactor design, and detection methods will be introduced. Combining with the powerful combinatorial methodology, good chemistry design will make our work even more efficient. Hence, as an example of combining combinatorial technologies with chemistry design, a successful catalyst design is also introduced. 相似文献
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Gauthier S Quebatte L Scopelliti R Severin K 《Chemistry (Weinheim an der Bergstrasse, Germany)》2004,10(11):2811-2821
Methods for the synthesis of bimetallic complexes in which two different metal fragments are connected by three chloro or bromo bridges are reported. The reactions are general, fast, and give rise to structurally defined products in quantitative yields. Therefore, they are ideally suited for generating a library of homo- and heterobimetallic complexes in a combinatorial fashion. This is of special interest for applications in homogeneous catalysis. Selected members of this library were synthesized and comprehensively characterized; single-crystal X-ray analyses were performed for 15 new bimetallic compounds. 相似文献
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A combinatorial library of 625 octapeptides was screened for their efficiency to catalyze phosphorester cleavage in water. Octapeptides such as 1c, which contains a catalytically active histidine and two cationic residues (Gua) as potential anion-binding sites, show substrate hydrolysis in water. Metal-free catalysis with a rate enhancement of up to a factor of 175 over the uncatalyzed background reaction is observed. 相似文献
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Herein we describe an algorithm for designing combinatorial peptide libraries for split-and-mix synthesis on solid support that are decodable by amino acid analysis (AAA) of the beads. AAA is a standard service analysis available in most biochemical laboratories, and it allows one to control the quality of the peptide on each bead, an important feature that is missing from most library decoding protocols. In the algorithm, each AA is assigned to two variable positions in the sequence grouped in a "unique pair". This arrangement limits sequence design because both the number of unique pairs U (setting the maximum number of variable AA) and the maximum number S of different AA per variable position depend on the peptide length N (U=N(N-1)/2), S=N-1). The method is therefore only suitable for focused libraries. An application example is shown for the selection of peptides with N-terminal proline or hydroxyproline catalyzing an aldol reaction from a combinatorial library of 65536 octapeptides. A simple enumeration program is available to help design combinatorial libraries decodable by amino acid analysis. The method applies to linear and cyclic peptides, can be used for nonnatural building blocks, including beta-amino acids, and should help to explore the vast chemistry of linear and cyclic peptide for catalysis and bioactivity. 相似文献
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Valdes-Perez RE Zeigarnik AV 《Journal of chemical information and computer sciences》2000,40(3):833-838
Most chemical reactions occur over multiple steps whose identity is elucidated by experiment, yielding a reaction mechanism. Knowledge of cognitive science suggests that mechanism elucidation can be viewed as a knowledge-guided search within a combinatorial space. The MECHEM computer program searches this space comprehensively for the simplest plausible mechanisms. We use MECHEM to find mechanisms for Fischer-Tropsch chemistry and CO2 re-forming of methane, both heterogeneous catalytic reactions of current importance. The results reveal hundreds of equally simple mechanisms consistent with evidence. Hence, mechanism elucidation in catalysis is a much harder problem than is ordinarily realized. 相似文献
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Affinity capillary electrophoresis is a new procedure for receptor-ligand binding studies. Since its introduction in the early 1990s, this method has proved valuable in chiral separation of racemates, the measurement of binding constants, the estimation of kinetic rate constants, the determination of stoichiometries, the investigation of electrostatic interactions, the estimation of effective charges and molecular weights of biomolecules, the characterization of enzymatic catalysis, and, most recently, combinatorial library screening in solutions. This technique demands small amounts of samples, involves no radiolabeled materials or chemically immobilized ligands, and does not require changes in spectroscopic characteristics upon binding. This paper reviews the most recent applications of affinity capillary electrophoresis in binding measurement and combinatorial library screening. 相似文献
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Two synthetically modified nucleoside triphosphate analogues (adenosine modified with an imidazole and uridine modified with a cationic amine) are enzymatically polymerized in tandem along a degenerate DNA library for the combinatorial selection of an RNAse A mimic. The selected activity is consistent with both electrostatic and general acid/base catalysis at physiological pH in the absence of divalent metal cations. The simultaneous use of two modified nucleotides to enrich the catalytic repertoire of DNA-based catalysts has never before been demonstrated and evidence of general acid/base catalysis at pH 7.4 for a DNAzyme has never been previously observed in the absence of a divalent metal cation or added cofactor. This work illustrates how the incorporation of protein-like functionalities in nucleic acids can bridge the gap between proteins and oligonucleotides underscoring the potential for using nucleic acid scaffolds in the development of new materials and improved catalysts for use in chemistry and medicine. 相似文献
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Reshetnyak AV Armentano MF Ponomarenko NA Vizzuso D Durova OM Ziganshin R Serebryakova M Govorun V Gololobov G Morse HC Friboulet A Makker SP Gabibov AG Tramontano A 《Journal of the American Chemical Society》2007,129(51):16175-16182
Reactivity-based selection strategies have been used to enrich combinatorial libraries for encoded biocatalysts having revised substrate specificity or altered catalytic activity. This approach can also assist in artificial evolution of enzyme catalysis from protein templates without bias for predefined catalytic sites. The prevalence of covalent intermediates in enzymatic mechanisms suggests the universal utility of the covalent complex as the basis for selection. Covalent selection by phosphonate ester exchange was applied to a phage display library of antibody variable fragments (scFv) to sample the scope and mechanism of chemical reactivity in a naive molecular library. Selected scFv segregated into structurally related covalent and noncovalent binders. Clones that reacted covalently utilized tyrosine residues exclusively as the nucleophile. Two motifs were identified by structural analysis, recruiting distinct Tyr residues of the light chain. Most clones employed Tyr32 in CDR-L1, whereas a unique clone (A.17) reacted at Tyr36 in FR-L2. Enhanced phosphonylation kinetics and modest amidase activity of A.17 suggested a primitive catalytic site. Covalent selection may thus provide access to protein molecules that approximate an early apparatus for covalent catalysis. 相似文献
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An efficient asymmetric catalyst relies on the successful combination of a large number of interrelated variables, including rational design, intuition, persistence, and good fortune-not all of which are necessarily well-understood; this renders such practice largely empirical. As a result, the possibility of using combinatorial chemistry methods in asymmetric catalysis research has been widely recognized to be highly desirable. In this account, we attempt to show the principle and application of combinatorial approach in the discovery of chiral catalysts for enantioselective reactions. The concept focuses on the strategy for the creation of a modular chiral catalyst library by two-component ligand modification of metal ions on the basis of molecular recognition and assembly. The self-assembled chiral catalyst with two different ligands indeed exhibited synergistic effects in terms of both enantioselectivity and activity in comparison with its corresponding homocombinations in many reactions. The examples described in this paper demonstrated the powerfulness of combinatorial approach for the discovery of novel chiral catalyst systems, particularly for the development of highly efficient, enantioselective, and practical catalysts for enantioselective reactions. We hope this concept will stimulate further work on the discovery of more highly efficient and enantioselective catalysts, as well as unexpected classes of catalysts or catalytic enantioselective reactions in the future with the help of a combinatorial chemistry approach. 相似文献