共查询到20条相似文献,搜索用时 15 毫秒
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A dynamic library of 15 mono- and bi-conjugated oligonucleotides was generated from a pool of three aldehydes and an oligonucleotide bearing two reactive amino groups. Addition of complementary target to the equilibrating mixture of imines resulted in selective amplification of one conjugate. UV-melting experiments confirmed that it was the best ligand among those that were tested. This study emphasizes that dynamic combinatorial chemistry can be used to simultaneously identify the type and the location of appended residues for stabilizing oligonucleotide complexes. 相似文献
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Kitade M Tanaka H Oe S Iwashima M Iguchi K Takahashi T 《Chemistry (Weinheim an der Bergstrasse, Germany)》2006,12(5):1368-1376
The solid-phase synthesis of a combinatorial cross-conjugated dienone library based on the structure of clavulones and their biological activity are reported. Clavulones are a family of marine prostanoids, and are composed of a cross-conjugated dienone system bearing two alkyl side-chains. The cross-conjugated dienone system irreversibly reacted with two nucleophiles. Our strategy for the solid-phase synthesis of the cross-conjugated dienones involves the Sonogashira-coupling reaction of a solid-supported cyclopentenone 10 bearing an acetylene group, followed by aldol condensation with aldehydes. The diphenyl derivative 7 aA was prepared from the solid-supported cyclopentenone 10 in 56% total yield. Combinatorial synthesis of a small library using twelve halides and eight aldehydes resulted in the production of 74 desired compounds from 98 candidates, and were detected by their mass spectra. Antiproliferative effects of the crude compounds against HeLaS3 cells showed that eleven samples showed strong antitumor activity (IC50<0.05 microM). Further biological examination of four purified compounds by using five tumor cell lines (A549, HeLaS3, MCF7, TMF1, and P388) revealed strong cytotoxicity comparable to that of adriamycin. 相似文献
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Graziella CappellettiDaniele Cartelli Bruno PerettoMicol Ventura Marco RiccioliFrancesco Colombo John S. SnaithStella Borrelli Daniele Passarella 《Tetrahedron》2011,67(38):7354-7357
The use of tubulin as a target to influence the composition of the mixture from a dynamic combinatorial library, based on the disulfide bond exchange reaction, is described. ESI-FT-ICR-MS was used to determine the composition of the library. The heterodimeric compound amplified by this approach was used to design the homologous derivative with a two-carbon spacer in place of the disulfide function. The ability of the compounds to inhibit tubulin polymerization is reported and compared to thiocolchicine. 相似文献
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Boger DL Desharnais J Capps K 《Angewandte Chemie (International ed. in English)》2003,42(35):4138-4176
The high-throughput synthesis and screening of compound libraries hold tremendous promise for drug discovery and powerful methods for both solid-phase and solution-phase library preparation have been introduced. The question of which approach (solution-phase versus solid-phase) is best for the preparation of chemical libraries has been replaced by which approach is most appropriate for a particular target or screen. Herein we highlight distinctions in the two approaches that might serve as useful considerations at the onset of new programs. This is followed by a more personal account of our own focus on solution-phase techniques for the preparation of libraries designed to modulate cellular signaling by targeting protein-protein or protein-DNA interactions. The screening of our libraries against a prototypical set of extracellular and intracellular targets, using a wide range of assay formats, provided the first small-molecule modulators of the protein-protein interactions studied, and a generalized approach for conducting such studies. 相似文献
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The first examples of dynamic combinatorial libraries of cryptands, created using the chemistry of imines is presented. Experiments, in which two trialdehydes compete for one triamine in a small library, show the full reversibility of cryptand formation, since the library composition is the same irrespective of the sequence of introducing the building blocks to the mixture. 相似文献
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Severin K 《Chemistry (Weinheim an der Bergstrasse, Germany)》2004,10(10):2565-2580
Numerical simulations are presented that describe the adaptive behavior of simple dynamic combinatorial libraries (DCLs) upon addition of a target. By studying the effect of various parameters such as the network topology, the initial concentrations, the association constants, and the binding affinities, general characteristics of such systems were derived. It is shown that the adaptation may lead to the amplification of molecules with a high affinity to the target, but only for specific boundary conditions. Furthermore, it is demonstrated that the selection process can be refined by using an evolutionary approach. These results are of importance for the design of selection experiments with DCLs. 相似文献
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This paper describes the generation of a dynamic combinatorial library of sialic acid analogues using sialic acid aldolase. Addition of wheat germ agglutinin to the equilibrating libraries results in selective amplification of one or more members. 相似文献
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The constitutional recomposition of a dynamic library of imines displays a complex behavior under the effect of two parameters, acidity and temperature. A qualitative analysis of the quantitative data is presented. The results illustrate the response of such a dynamic system to a physical stimulus (temperature) and a chemical effector (H+), thus demonstrating its adaptive behavior under the pressure of external factors. They also point to the possibility of modulating a given functional property (optical, electronic, ionic) by constitutional recomposition induced by a specific trigger. Such features are of great interest for the development of stimuli-responsive, functional dynamic materials. 相似文献
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López-Senín P Gómez-Pinto I Grandas A Marchán V 《Chemistry (Weinheim an der Bergstrasse, Germany)》2011,17(6):1946-1953
We describe the use of dynamic combinatorial chemistry (DCC) to identify ligands for the stem-loop structure located at the exon 10-5'-intron junction of Tau pre-mRNA, which is involved in the onset of several tauopathies including frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). A series of ligands that combine the small aminoglycoside neamine and heteroaromatic moieties (azaquinolone and two acridines) have been identified by using DCC. These compounds effectively bind the stem-loop RNA target (the concentration required for 50% RNA response (EC(50)): 2-58 μM), as determined by fluorescence titration experiments. Importantly, most of them are able to stabilize both the wild-type and the +3 and +14 mutated sequences associated with the development of FTDP-17 without producing a significant change in the overall structure of the RNA (as analyzed by circular dichroism (CD) spectroscopy), which is a key factor for recognition by the splicing regulatory machinery. A good correlation has been found between the affinity of the ligands for the target and their ability to stabilize the RNA secondary structure. 相似文献
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A cyclic porphyrin tetramer, consisting of two bis-phosphine substituted zinc(II) porphyrin units and two Rh(III)TPP units, is selected and amplified virtually quantitatively from a dynamic combinatorial library using 4,4'-bipy as a scaffold and using orthogonal binding modes. 相似文献
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Dynamic combinatorial libraries were generated incorporating new pyridine and dimethylaniline containing monomers. These libraries were analyzed using 1H NMR and HPLC–UV–MS. 相似文献