共查询到20条相似文献,搜索用时 31 毫秒
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Smitha VokkaligaJeannie Jeong William R. LaCourse Aristotle Kalivretenos 《Tetrahedron letters》2011,52(21):2722-2724
Highly reactive N-acylating solid-phase reagents based on macroporous polystyrene-bound 1-hydroxybenzotriazole (P-HOBt) and silica-bound 1-hydroxybenzotriazole (Si-HOBt) were prepared and compared for reactivity by synthesis of small combinatorial libraries of acetamides and benzamides. 相似文献
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A possibility of using polyfluorinated pyridines as multiply modified molecules, i.e., scaffolds, in processes of aromatic nucleophilic substitution (S
N
Ar) for the synthesis of liquid-phase combinatorial libraries was studied. The real and “virtual” combinatorial libraries of
diaryl ethers were synthesized by the reactions of pentafluoropyridine with phenol and its derivatives. Some criteria for
the estimation of the quality of the libraries were formulated. A rational methodology for the preparation of representative
combinatorial mixtures on the basis of processes of the S
N
Ar type in polyfluorinated arenes was proposed. The libraries can be used in highly efficient biological screening of low-molecular-weight
regulators of transferase functioning.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 945–950, May, 2007. 相似文献
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Comparison of bacterial and phage display peptide libraries in search of target-binding motif 总被引:1,自引:0,他引:1
Lunder M Bratkovic T Doljak B Kreft S Urleb U Strukelj B Plazar N 《Applied biochemistry and biotechnology》2005,127(2):125-131
Genetic engineering allows modification of bacterial and bacteriophage genes, which code for surface proteins, enabling display
of random peptides on the surface of these microbial vectors. Biologic peptide libraries thus formed are used for high-throughput
screening of clones bearing peptides with high affinity for target proteins. There are reports of many successful affinity
selections performed with phage display libraries and substantially fewer cases describing the use of bacterial display systems.
In theory, bacterial display has some advantages over phage display, but the two systems have never been experimentally compared.
We tested both techniques in selecting streptavidin-binding peptides from two commercially available libraries. Under similar
conditions, selection of phage-displayed peptides to model protein streptavidin proved convincingly better. 相似文献
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Mami Tojino 《Tetrahedron letters》2008,49(41):5920-5923
The synthesis of an oligosaccharide library by a fluorous tag method is reported here. Several acceptors and donors were mixed and glycosylated. The reaction mixture was purified by chromatography over fluorous HPLC to provide disaccharides in order of increasing fluorine content of the tag. This method could be applied to oligosaccharide libraries consisting of two sets of structural isomers. 相似文献
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Chamakura V VaraprasadQazi Habib David Y LiJingfan Huang Jeffrey W AbtFrank Rong Zhi HongHaoyun An 《Tetrahedron》2003,59(13):2297-2307
A versatile parallel solid-phase combinatorial strategy was developed for the synthesis of large nucleoside libraries. Twelve libraries L1-12 of 1152 novel exocyclic triazinylamino nucleosides and one library L13 of 82 new substituted clitocine derivatives were synthesized in high quality as natural product mimic nucleosides on the semi-automated synthesizer. The polystyrene MMT-Cl resin was selected and utilized. The key intermediate resins 5 and 9 loaded with the corresponding scaffolds were prepared and validated with various amines before parallel synthesis. After a variety of amino building blocks were validated, 56 primary amines in 12 groups (building block set A) and 24 secondary amines in 3 groups (building block set B) were selected and utilized to combinatorialize the first and the second reactive sites on scaffold 5 for the synthesis of libraries L1-12. Eighty-two amines (building block set C) were utilized for the synthesis of clitocine library L13. Thirteen libraries of 1234 novel exocyclic amino nucleosides were all analyzed and characterized by high throughput LC-MS. 81.3-100% of the library members in 13 libraries show more than 60% purity, and 65.7-92.7% of the library members in these libraries show 80-100% purity. The strategy can be widely used for the synthesis of other diverse nucleoside libraries. 相似文献
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随着计算技术的发展和分子模拟软件的日趋成熟, 虚拟筛选已经在药物发现过程中发挥着越来越重要的作用. 在虚拟筛选过程中, 所使用化合物库的质量对先导化合物发现的成功率起着至关重要的作用. 本文通过对已知药物库、天然产物库、中药原植物化学成分库、筛选常用商业化合物库以及研究者所在实验室建立的化合物库的分析比较, 从化合物库的分子多样性、化学空间和分子骨架等多个方面提取并对比每一种化合物库的特征, 发现了已知药物库与中药原植物化学成分库的特征相似性, 揭示了中药原植物化学成分库作为筛选库的类药性优势, 并且深化了对几种筛选用化合物库特征的认识和理解. 相似文献
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Zhao R Fanga C Yu X Liu Y Luo J Shangguan D Xiong S Su T Liu G 《Journal of chromatography. A》2005,1064(1):59-66
The affinity inhibitor of fusion peptide of influenza A virus has been studied using a combination of high-performance affinity chromatography (HPAC) and combinatorial peptide libraries. Fusion peptide (FP) (1-11) of influenza A virus was used as the affinity ligand and immobilized onto the poly(glycidyl methacrylate) (PGMA) beads. Positional scanning peptide libraries based on antisense peptide strategy and extended peptide libraries were designed and synthesized. The screening was carried out at acidic pH (5.5) in order to imitate the environment of virus fusion. A hendecapeptide FHRKKGRGKHK was identified to have a strong affinity to the FP (1-11). The dissociation constant of the complex of the hendecapeptide and the FP (1-11) is 3.10 x 10(-6) mol l(-1) in a physiological buffer condition. The polypeptide has a fairly inhibitory effect on three different strains of influenza A virus H1N1 subtype. 相似文献
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Dr. Benjamin Zagiel Dr. Taleen Peker Dr. Rodrigue Marquant Guillaume Cazals Gabrielle Webb Dr. Emeric Miclet Dr. Claudia Bich Dr. Emmanuelle Sachon Dr. Roba Moumné 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(36):e202200454
An efficient strategy for the synthesis of large libraries of conformationally defined peptides is reported, using dynamic combinatorial chemistry as a tool to graft amino acid side chains on a well-ordered 3D (3-dimension) peptide backbone. Combining rationally designed scaffolds with combinatorial side chains selection represents an alternative method to access peptide libraries for structures that are not genetically encodable. This method would allow a breakthrough for the discovery of protein mimetic for unconventional targets for which little is known. 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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在无机磷试剂辅助下建立了氨基酸自组装成均环肽的方法, 得到了相应的均环肽库. 均环肽库的建立增加了肽库的多样性, 为药物筛选提供了新的选择性. 采用电喷雾多级质谱技术, 对系列均环多肽 [M+H]+离子和[M+Na]+离子的质谱裂解规律进行了系统研究, 两种系列的离子具有不同的质谱裂解特征, 分别提出了其可能的质谱裂解机制. 该研究丰富了环多肽化合物的电喷雾多级质谱研究, 结果表明环肽化合物的加钠离子较加氢离子的质谱图可以更容易地用于环多肽的序列测定. 本研究为其它类似环肽化合物结构的分析鉴定及利用电喷雾质谱推测环肽序列提供了有效的质谱方法. 相似文献
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在肽库中进行小肽筛选的初步研究 总被引:1,自引:0,他引:1
以合成六肽DGGSAA为模型对在噬菌体肽库中进行小肽筛选做了初步研究。结果表明,含有可形成氢键和离子键残基的小肽能够在噬菌体肽库中进行筛选。并用明显提高了筛选的专一性。 相似文献
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Artem B. Mamonov Xin Zhang Daniel M. Zuckerman 《Journal of computational chemistry》2011,32(3):396-405
We adapted existing polymer growth strategies for equilibrium sampling of peptides described by modern atomistic forcefields with a simple uniform dielectric solvent. The main novel feature of our approach is the use of precalculated statistical libraries of molecular fragments. A molecule is sampled by combining fragment configurations—of single residues in this study—which are stored in the libraries. Ensembles generated from the independent libraries are reweighted to conform with the Boltzmann‐factor distribution of the forcefield describing the full molecule. In this way, high‐quality equilibrium sampling of small peptides (4–8 residues) typically requires less than one hour of single‐processor wallclock time and can be significantly faster than Langevin simulations. Furthermore, approximate, clash‐free ensembles can be generated for larger peptides (up to 32 residues in this study) in less than a minute of single‐processor computing. We discuss possible applications of our growth procedure to free energy calculation, fragment assembly protein‐structure prediction protocols, and to “multi‐resolution” sampling. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011 相似文献
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A very large diversity space of synthetically accessible compounds for use with drug design programs
Nikitin S Zaitseva N Demina O Solovieva V Mazin E Mikhalev S Smolov M Rubinov A Vlasov P Lepikhin D Khachko D Fokin V Queen C Zosimov V 《Journal of computer-aided molecular design》2005,19(1):47-63
We have constructed a very large virtual diversity space containing more than 1013 chemical compounds. The diversity space is built from about 400 combinatorial libraries, which have been expanded by choosing sizeable collections of suitable R-groups that can be attached to each link point of their scaffolds. These R-group collections have been created by selecting reagents that have drug-like properties from catalogs of available chemicals. As members of known combinatorial libraries, the compounds in the diversity space are in general synthetically accessible and useful as potential drug leads. Hence, the diversity space can be used as a vast source of compounds by a de novo drug design program. For example, we have used such a program to generate inhibitors of HIV integrase enzyme that exhibited activity in the micromolar range. 相似文献
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Selection of DNA‐Encoded Small Molecule Libraries Against Unmodified and Non‐Immobilized Protein Targets 下载免费PDF全文
Peng Zhao Zitian Chen Yizhou Li Dawei Sun Yuan Gao Prof. Yanyi Huang Prof. Xiaoyu Li 《Angewandte Chemie (International ed. in English)》2014,53(38):10056-10059
The selection of DNA‐encoded libraries against biological targets has become an important discovery method in chemical biology and drug discovery, but the requirement of modified and immobilized targets remains a significant disadvantage. With a terminal protection strategy and ligand‐induced photo‐crosslinking, we show that iterated selections of DNA‐encoded libraries can be realized with unmodified and non‐immobilized protein targets. 相似文献
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Selahattin Ede Mandy Schenk Donald Bierer Hilmar Weinmann Keith Graham 《Molecules (Basel, Switzerland)》2021,26(6)
DNA-encoded libraries (DEL) are increasingly being used to identify new starting points for medicinal chemistry in drug discovery. Herein, we discuss the development of methods that allow the conversion of both primary amines and anilines, attached to DNA, to their corresponding azides in excellent yields. The scope of these diazo-transfer reactions was investigated, and a proof-of-concept has been devised to allow for the synthesis of macrocycles on DNA. 相似文献
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Dillon T. Flood Xuejing Zhang Xiang Fu Zhenxiang Zhao Shota Asai Brittany B. Sanchez Emily J. Sturgell Julien C. Vantourout Paul Richardson Mark E. Flanagan David W. Piotrowski Dominik K. Klmel Jinqiao Wan Mei‐Hsuan Tsai Jason S. Chen Phil S. Baran Philip E. Dawson 《Angewandte Chemie (International ed. in English)》2020,59(19):7377-7383
DNA encoded libraries (DEL) have shown promise as a valuable technology for democratizing the hit discovery process. Although DEL provides relatively inexpensive access to libraries of unprecedented size, their production has been hampered by the idiosyncratic needs of the encoding DNA tag relegating DEL compatible chemistry to dilute aqueous environments. Recently reversible adsorption to solid support (RASS) has been demonstrated as a promising method to expand DEL reactivity using standard organic synthesis protocols. Here we demonstrate a suite of on‐DNA chemistries to incorporate medicinally relevant and C?S, C?P and N?S linkages into DELs, which are underrepresented in the canonical methods. 相似文献