Combinatorial Library Based on the One‐Bead‐One‐Compound Concept

Lam, Kit S.; Lebl, Michal

doi:10.1002/9783527614912.ch06

Cited by 8 publications

(4 citation statements)

References 81 publications

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“…An on-bead binding assay is a fruitful method for the screening of libraries as it allows efficient and rapid detection of lead compounds . Particular attention should be focused on the biological tests performed on the on-resin libraries of 4-sulfamoylphenylthioureas in order to obtain screening results comparable to our standard CA inhibitory assays in solution .…”

Section: Discussionmentioning

confidence: 99%

“…An on-bead binding assay is a fruitful method for the screening of libraries as it allows efficient and rapid detection of lead compounds. 15 Particular attention should be focused on the biological tests performed on the on-resin libraries of 4-sulfamoylphenylthioureas in order to obtain screening results comparable to our standard CA inhibitory assays in solution. 10 Therefore, this work deals with the optimization of the parameters involved in the synthetic pathway and in the biological tests, for further setup and high-throughput on-resin screening of libraries of 4-sulfamoylphenylthioureas derivatized with single amino acids or with oligopeptide residues.…”

Section: Carbonic Anhydrase Inhibitorsmentioning

confidence: 99%

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Carbonic Anhydrase Inhibitors: The First On-Resin Screening of a 4-Sulfamoylphenylthiourea Library

et al. 2004

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Sulfonamide carbonic anhydrase (CA) inhibitors are widely employed in the diagnosis and treatment of diverse diseases such as glaucoma and different neuromuscular disorders. Moreover, an emerging area is represented by their use in the prevention and treatment of tumors. In this paper we propose an optimized synthesis of on-resin CA inhibitor libraries to be used for a high-throughput biological screening. A library of 4-sulfamoylphenylthioureas, previously described to be attractive candidates as novel antiglaucoma drugs, has been synthesized by a solid-phase approach, avoiding the formation of thiohydantoin side products. The on-resin screening assay has been developed for the inhibition tests of different CA isozymes with the on-resin supported sulfonamides, allowing the direct identification of the biologically active lead compounds. These results allow the development of new designed libraries in the solid phase of sulfonamide CA inhibitors characterized by a set of prefixed parameters to be used as possible drug candidates.

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Section: Discussionmentioning

confidence: 99%

Section: Carbonic Anhydrase Inhibitorsmentioning

confidence: 99%

Carbonic Anhydrase Inhibitors: The First On-Resin Screening of a 4-Sulfamoylphenylthiourea Library

et al. 2004

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“…Since the application of these OBOC libraries was reviewed [23,[236][237][238][239][240][241][242][243][244][245][246][247][248][249][250][251] on a number of occasions and in a multitude of journals and monographs, this chapter will not go into the individual results achieved with OBOC libraries (as listed, for example, in [252]), but rather concentrate on the various techniques applicable for their production and testing. Results achieved by Lams laboratory, which remains very active in developing OBOC technology and applying it especially in the area of cancer research, are available at http://oboc.ucdavis.edu/html/publications.htm.…”

Section: Synthesis Of Peptides On a Mixture Of Particlesmentioning

confidence: 99%

Combinatorial/Library Peptide Synthesis

Lebl

2011

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…One-bead one-compound (OBOC) combinatorial libraries are traditionally screened with tagged purified protein [1][2][3][4][5][6][7]. More recently, we reported the development of an enzyme-linked colorimetric subtraction screening method to probe OBOC libraries with complex protein mixtures [8].…”

Section: Introductionmentioning

confidence: 99%

Screening of a one bead–one compound combinatorial library for β-actin identifies molecules active toward Ramos B-lymphoma cells

Miyamoto

Liu

Hung

et al. 2008

Analytical Biochemistry

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The search for small molecules that specifically recognize protein targets is a laborious process if conducted in a one protein-one compound manner. A high-throughput antibody-based screening of one bead-one compound (OBOC) combinatorial small molecule libraries is described here, whereby libraries containing thousands of different small molecule ligands are synthesized on individual TentaGel beads and simultaneously screened for protein binding to individual beads, each with a different compound. The use of OBOC libraries greatly facilitates this simultaneous screening of thousands of compounds. Now, through the use of monoclonal or affinity-purified antibodies, small molecules that bind a particular protein contained in a complex mixture of biological molecules have been identified. This method identified small molecule ligands that bound beta-actin present in cytoplasmic cell extracts of Ramos B-lymphoma cells. These small molecule ligands were resynthesized in immobilized and soluble forms and tested for binding of beta-actin present in Ramos B-cell extracts and for activity against Ramos lymphoma cells. This high-throughput screening immunoassay method has great promise for improving our ability to find relevant, bioactive small molecules that target a specific native protein in a complex protein mixture without purification of the protein.

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Combinatorial Library Based on the One‐Bead‐One‐Compound Concept

Cited by 8 publications

References 81 publications

Carbonic Anhydrase Inhibitors: The First On-Resin Screening of a 4-Sulfamoylphenylthiourea Library

Carbonic Anhydrase Inhibitors: The First On-Resin Screening of a 4-Sulfamoylphenylthiourea Library

Combinatorial/Library Peptide Synthesis

Screening of a one bead–one compound combinatorial library for β-actin identifies molecules active toward Ramos B-lymphoma cells

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