"Diversomers": an approach to nonpeptide, nonoligomeric chemical diversity.

DeWitt, Sheila; Kiely, John S.; Stankovic, Charles J.; Schroeder, Mel C.; Cody, Donna M. Reynolds; Pavia, Michael R.

doi:10.1073/pnas.90.15.6909

Cited by 335 publications

(112 citation statements)

References 26 publications

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“…[9][10][11]; (ii) spatially addressable syntheses in which the structure of a compound is deduced from its position on an array (2,(12)(13)(14); and (iii) split synthesis procedures, whereby compounds are built up on solid-phase beads, each of which has a unique history throughout the randomization steps and hence a unique structure-e.g., "one-bead-one-peptide" (4,6). The appropriate synthetic strategies can be modified in a number of ways so that with each component introduced by a combinatorial step, a conjugate "tag" is added in a parallel step; these coding sequences or tags are read subsequently to decode the steps used for the construction of the structure on any given bead.…”

mentioning

confidence: 99%

Enzyme-mediated spatial segregation on individual polymeric support beads: application to generation and screening of encoded combinatorial libraries.

Vagner

Bárány

Lam

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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Proteolysis of short NO-protected peptide substrates bound to polyoxyethylene-polystyrene beads releases selectively free amino sites in the enzyme-accessible "surface" area, The substantial majority of functional sites in the "interior" of the polymeric support are not reached by the enzyme and remain uncleaved (protected). Subsequent synthesis with two classes of orthogonal protecting groupsNa_tert-butyloxycarbonyl (Boc) and Na_9-fluorenylmethyloxycarbonyl (Fmoc)-allows generation of two structures on the same bead. The surface structure is available for receptor interactions, whereas the corresponding interior structure is used for coding. Coding structures are usually readily sequenceable peptides. This "shaving" methodology was illustrated by the preparation of a peptide-encoded model peptide combinatorial library containing 1.0 x 105 members at -6-fold degeneracy. From this single library, good ligands were selected for three different receptors: anti-.8-endorphin antibody, streptavidin, and thrombin, and the binding structures were deduced correctly by sequencing the coding peptides present on the same beads.

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mentioning

confidence: 99%

Enzyme-mediated spatial segregation on individual polymeric support beads: application to generation and screening of encoded combinatorial libraries.

Vagner

Bárány

Lam

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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“…3,4 Pilot experiments were initiated utilizing commercially available FMOC-glycine as a source of DBF. However, it was found that addition of 20% piperidine/DMF to this compound formed a precipitate (presumably piperidinium glycinate), which could potentially complicate analysis.…”

Section: Resultsmentioning

confidence: 99%

Analysis of 9-fluorenylmethoxycarbonyl (FMOC) loading of solid-phase synthesis resins by gas chromatography

Newcomb¹,

Deegan²,

Miller³

et al. 1998

Biotechnol. Bioeng.

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“…A common strategy in solid-phase synthesis is cyclization-assisted cleavage which combines the linker cleavage and ring formation in a single reaction step [57]. One of the first examples of cyclative cleavage of polymer support in solid-phase synthesis was developed in the preparation of hydantoins [58].…”

Section: Introductionmentioning

confidence: 99%

Fluorous parallel synthesis of a hydantoin/thiohydantoin library

Zhang

2005

Mol Divers

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Fluorous tagging strategy is applied to solution-phase parallel synthesis of a library containing hydantoin and thiohydantoin analogs. Two perfluoroalkyl (Rf)-tagged α-amino esters each react with 6 aromatic aldehydes under reductive amination conditions. Twelve amino esters then each react with 10 isocyanates and isothiocyanates in parallel. The resulting 120 ureas and thioureas undergo spontaneous cyclization to form the corresponding hydantoins and thiohydantoins. The intermediate and final product purifications are performed with solid-phase extraction (SPE) over FluoroFlash™ cartridges, no chromatography is required. Using standard instruments and straightforward SPE technique, one chemist accomplished the 120-member library synthesis in less than 5 working days, including starting material synthesis and product analysis.

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"Diversomers": an approach to nonpeptide, nonoligomeric chemical diversity.

Cited by 335 publications

References 26 publications

Enzyme-mediated spatial segregation on individual polymeric support beads: application to generation and screening of encoded combinatorial libraries.

Enzyme-mediated spatial segregation on individual polymeric support beads: application to generation and screening of encoded combinatorial libraries.

Analysis of 9-fluorenylmethoxycarbonyl (FMOC) loading of solid-phase synthesis resins by gas chromatography

Fluorous parallel synthesis of a hydantoin/thiohydantoin library

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