Production, Analysis, and Application of Spatially Resolved Shells in Solid-Phase Polymer Spheres

Farrer, Richard A.; Copeland, Gregory T.; Previte, Michael J. R.; Okamoto, Mariko M.; Miller, Scott J.; Fourkas, John T.

doi:10.1021/ja011675k

Cited by 36 publications

(33 citation statements)

References 22 publications

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“…Since the library compound on the bead surface does not have a cleavable linker, it will never be released and will not affect the MS analysis. 17 The method is based on the fact that the reaction rate of amino protection is significantly faster than the diffusion rate of the protecting agent inside the bead. However, as indicated by the authors in the article, as the synthesis of each layer progresses, the production of each successive layer becomes more difficult.…”

Section: Resultsmentioning

confidence: 99%

Partial Alloc-Deprotection Approach for Ladder Synthesis of “One-Bead One-Compound” Combinatorial Libraries

Wang

Liu

et al. 2005

J. Comb. Chem.

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The topologically segregated bilayer-bead concept has been applied to encoded "one-bead one-compound"(OBOC) combinatorial libraries to avoid the interference of coding tags with biological screening. In this paper, we report on the development of a novel partial Alloc-deprotection (PAD) approach and the use of this approach to establish a new ladder-synthesis method for OBOC combinatorial libraries to further exploit the concept. In the PAD approach, Alloc-protected beads are partially deprotected, sequentially layer by layer, starting from the outer layer toward the bead interior. The degree of deprotection (or thickness of each layer) is controlled by the time of exposure to the deprotecting agent, palladium. By repetitive use of the PAD approach, a small portion of Alloc-protected N termini in the bead interior is liberated in each synthetic cycle for generation of an additional ladder member such that each library bead will carry a full-length library compound on the bead surface and a series of truncated ladder members in the bead interior. For the libraries containing isobaric residues, a simple encoding strategy is introduced in the ladder-synthesis method so that the isobaric residues can be differentiated by the coding tags. One advantage of this encoding strategy is that the coding tags are confined together with the truncated ladder members in the bead interior, thus maintaining the arrangement that only the library compounds are displayed on the bead surface. The PAD approach of forming multiple concentric functional layers inside a bead is simple, reliable, and may have other applications in addition to OBOC combinatorial library bead encoding, such as the development of novel optically encoded beads for multiplex immunodiagnostics or even information recording.

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Section: Resultsmentioning

confidence: 99%

Partial Alloc-Deprotection Approach for Ladder Synthesis of “One-Bead One-Compound” Combinatorial Libraries

Wang

Liu

et al. 2005

J. Comb. Chem.

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“…Farrer et al have reported the generation of multi-layer beads using a chemical method similar to our PAP approach by employing Fmoc-chloride [45]. Concentric bead layers were produced by means of sequential protection and deprotection of the primary amines within the beads.…”

Section: Methods For Generating Topologically Segregated Bilayer Beadsmentioning

confidence: 99%

Development and Applications of Topologically Segregated Bilayer Beads in One-bead One-compound Combinatorial Libraries

Liu¹,

Wang²,

Song³

et al. 2005

QSAR Comb. Sci.

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Using a "split -mix" synthesis approach, "One-Bead One-Compound" (OBOC) combinatorial libraries can be generated such that each bead displays only one chemical entity.Tens of thousands to millions of compound-beads can be screened concurrently using a variety of biochemical and cell-based screening methods. Positive beads are then physically isolated for structure determination. Peptide beads or peptoid beads consisting of a-amino acids and with a free N-terminus can be routinely sequenced by an automatic microsequencer using Edman chemistry. Libraries with N-terminally blocked peptides, peptides with unsequenceable building blocks, or small molecules require encoding. To fully exploit the OBOC combinatorial library methods, we have developed topologically segregated bilayer beads. Such bilayer beads allow us to prepare library compound on the outer layer of each bead and the coding tags in the bead interior. In addition, we can use these bilayer beads to prepare OBOC combinatorial libraries that are down-substituted on the bead surface but fully substituted in the bead interior. This configuration enables one to screen at a much higher stringency and yet have enough peptides or coding tags retained in the bead interior for structure determination.

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“…The homogeneity of the loading of the particles was determined by coupling dansyl chloride to the free amine groups followed by analysis using a two-photon microscope [13]. The results of this work are shown in figures 4 and 5.…”

Section: Stirrermentioning

confidence: 98%

Making PEG-based Microparticles for Applications in Biology and Medicine

McDonald

Christensen²,

Ulijn

2007

MRS Proc.

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Production, Analysis, and Application of Spatially Resolved Shells in Solid-Phase Polymer Spheres

Cited by 36 publications

References 22 publications

Partial Alloc-Deprotection Approach for Ladder Synthesis of “One-Bead One-Compound” Combinatorial Libraries

Partial Alloc-Deprotection Approach for Ladder Synthesis of “One-Bead One-Compound” Combinatorial Libraries

Development and Applications of Topologically Segregated Bilayer Beads in One-bead One-compound Combinatorial Libraries

Making PEG-based Microparticles for Applications in Biology and Medicine

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