Organogel media for on-bead screening in combinatorial catalysis

Johansson, Karl-Jonas; Andreae, Marc R. M.; Berkessel, Albrecht; Davis, Anthony P.

doi:10.1016/j.tetlet.2005.03.125

Cited by 20 publications

(16 citation statements)

References 29 publications

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“…These methods hold promise for catalyst discovery from split-and-mix combinatorial libraries. 12 Metal complexes of C 2 -symmetric Lewis acid/Lewis base salen ligands provide bifunctional activation resulting in rapid rates in the enantioselective addition of diethylzinc to aldehydes (up to 92% ee). A library of the bifunctional amino salens has been synthesised and evaluated in this reaction.…”

Section: Library Applicationsmentioning

confidence: 99%

Combinatorial Chemistry Online

Terrett

2005

Combinatorial Chemistry - an Online Journal

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Current literature highlights Tight-Binding Inhibitors of a-FucosidaseCompounds containing glycosidic bonds are involved in a number of biological and disease processes such as metabolic disorders, viral and bacterial infection and tumour growth and metastasis. As the glycosidic bonds are cleaved by glycosidases, these enzymes are considered important therapeutic targets. Potent glycosidase inhibitors have been sought to treat disease, such as the neuraminidase inhibitor Tamiflu TM and oseltamivir phosphate TM , prescribed to treat influenza virus infection.Amongst members of the glycosidase family, a-fucosidase is involved in removal of nonreducing terminal L L-fucose residues that are connected to oligosaccharides via a1,2-, a1,3-, a1,4-, or a1,6-linkages. Due to the great variety of physiological and pathological events associated with fucose-containing glycoconjugates, certain a-fucosidases have attracted the attention of researchers. An aberrant distribution of a-fucosidases is associated with inflammation, cancer and cystic fibrosis, and these enzymes are recognised as diagnostic markers for the early detection of colorectal and hepatocellular cancers because of the presence of a-fucosidase in the patientsÕ sera. Recently, slow and tight binding inhibitors of afucosidase have been discovered using a combinatorial chemistry approach. 1 This work centred on screening for an optimal aglycon attached to a fuconojirimycin (FNJ)-based structure (i). These FNJ-based structures mimic the transition state of enzymatic glycosidase cleavage.Using 1-aminomethyl FNJ (ii) as the scaffold for diversity-orientated synthesis, a library of amides was prepared by reaction with carboxylic acids. The library compounds were screened without purification, and several potent and competitive inhibitors against a-fucosidase from Corynebacterium sp. were discovered with IC 50 values in the low nM range, including compound (iii) with a K i value of 0.32 nM. It was observed that during prolonged observation of the enzyme inhibition assay there was a time-dependent decrease in the reaction rate as a function of the inhibitor concentration. Upon re-synthesis and purification of a number of library members exhibiting this time-dependent phenomenon, it was shown that the initial collision-complex (E AE I) isomerises to a tighter complex (E AE I*), where E represents free enzyme, I is free inhibitor, E AE I is a rapidly forming preequilibrium complex and E AE I* is the final enzyme-inhibitor complex.Rapid diversity-based synthesis and subsequent in situ screening enables rapid identification of suitable hydrophobic groups that enhance inhibition. Further work to determine the structure of the enzyme-inhibitor complex, allowing an understanding of the mechanism of inhibition is warranted, and the slow-releasing feature of the inhibition process could also provide new directions in drug design.

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Section: Library Applicationsmentioning

confidence: 99%

Combinatorial Chemistry Online

Terrett

2005

Combinatorial Chemistry - an Online Journal

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“…Apart from the few hydrogels listed above, there are no examples of organogels as scaffolds, despite the intensive research induced by the potential application of organogels as organic soft materials [24][25][26][27][28][29]. Nevertheless, these materials seem to be adapted for reconstruction of soft tissues that present the majority of biological tissue structures (for example, different types of connective tissues).…”

Section: Introductionmentioning

confidence: 99%

Preparation and evaluation of microporous organogel scaffolds for cell viability and proliferation

Lukyanova

Franceschi‐Messant

Vicendo

et al. 2010

Colloids and Surfaces B: Biointerfaces

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“…One of the efficient screening systems for multiple heterogeneous samples is a noncontact measurement of temperatures in reaction mixtures, which typically rise with the reaction courses. 9,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Crivello and coworkers [20][21][22][23][24][25][26][27] have established a facile and reproducible analytical method for the photoinitiated polymerization of various monomers. From this point of view, we have preliminarily investigated (co)polymerizations of SOE and oxetane monomers with thermally latent sulfonium salts.…”

Section: Introductionmentioning

confidence: 99%

Novel analytical method for the crosslinking process: Infrared thermographic analysis of the thermally latent cationic polymerization of a spiroorthoester and a bifunctional oxetane for the construction of a low‐shrinkage curing system

Ochiai

Nagasawa

Asano

et al. 2007

J. Polym. Sci. A Polym. Chem.

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Thermal behaviors were monitored by infrared thermographic analysis in the copolymerization of a spiroorthoester and a bifunctional oxetane with thermally latent initiators [benzyl tetrahydrothiophenium hexafluoroantimonate (BTHT) and benzyl 4-hydroxyphenyl methyl sulfonium hexafluoroantimonate (BPMS)]. The copolymerization with BPMS increased the temperature during the copolymerization more than that with BTHT, whereas the exothermicities were lowered with the increase in the initial feed ratio of the spiroorthocarbonate monomer. The high exothermicity in the copolymerization with BPMS is ascribable to the faster propagation of the oxetane monomer with a high heat of polymerization, and this is supported by model reactions and computational calculation.

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Organogel media for on-bead screening in combinatorial catalysis

Cited by 20 publications

References 29 publications

Combinatorial Chemistry Online

Combinatorial Chemistry Online

Preparation and evaluation of microporous organogel scaffolds for cell viability and proliferation

Novel analytical method for the crosslinking process: Infrared thermographic analysis of the thermally latent cationic polymerization of a spiroorthoester and a bifunctional oxetane for the construction of a low‐shrinkage curing system

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