Nonsequenceable and/or nonpeptide libraries

Lebl, Michal; Krchňák, Viktor; Stierandová, Alena; Safar, Pavel; Kočiš, Petr; Nikolaev, Victor; Sepetov, Nikolai F.; Ferguson, R. D.; Seligmann, Bruce; Lam, K. S.; Salmon, Sydney E.

doi:10.1007/978-94-011-0683-2_340

Cited by 11 publications

(21 citation statements)

References 1 publication

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“…To eliminate such interference, the coding tags should be confined in the bead interior. We have previously reported generating topologically segregated bi-functional beads by using polyglutamic acid [41] or proteases [41,42], to modi- We have recently developed a simple, inexpensive, and highly reproducible bi-phasic solvent approach to topologically segregate resin beads [43]. We called this method the "Partial Amine-Protection (PAP)" bilayer approach.…”

Section: Methods For Generating Topologically Segregated Bilayer Beadsmentioning

confidence: 98%

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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Section: Methods For Generating Topologically Segregated Bilayer Beadsmentioning

confidence: 98%

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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show abstract

“…The synthetic approach, however, offers the ability to incorporate into libraries unnatural amino acids, disulfide and nondisulfide cyclic structures, reduced peptide bonds, nonpeptide moieties, and specialized linkers (scaffolds) on which to attach the subunits, departing from the sequential arrangement of subunits.5,8,67. [69][70][71][72][73][74][75][76] Quality control of libraries can also be performed prior to screening. This can be accomplished by sequencing randomly chosen beads or by multiple sequencing of a ample.^' Amino acid analysis can be performed as well as mass spectroscopic evaluation of the sample of the cleaved lib r a r~.~~ In all cases a statistically relevant sample must be evaluated.…”

Section: Structure Librariesmentioning

confidence: 99%

One‐bead–one‐structure combinatorial libraries

Lebl

Krchňák²,

Sepetov³

et al. 1995

Biopolymers

134

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Combinatorial libraries employing the one-bead-one-compound technique are reviewed. Two distinguishing features characterize this technique. First, each compound is identified with a unique solid support, enabling facile segregation of active compounds. Second, the identity of a compound on a positively reacting bead is elucidated only after its biological relevance is established. Direct methods of structure identification (Edman degradation and mass spectroscopy) as well as indirect "coding" methods facilitating the synthesis and screening of nonpeptide libraries are discussed. Nonpeptide and "scaffold" libraries, together with a new approach for the discovery of a peptide binding motif using a "library of libraries," are also discussed. In addition, the ability to use combinatorial libraries to optimize initially discovered leads is illustrated with examples using peptide libraries.

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“…One-bead-one-compound technology is not limited to linear peptides attached via carboxy terminus. Solid phase methodology makes possible the preparation and testing of all types of cyclized peptides [219][220][221] , or peptides attached via amino terminus or via an amino acid side chain [222][223][224] .…”

Section: One-bead-one-structure Librariesmentioning

confidence: 99%

“…In following screening of secondary, tertiary and quaternary libraries the most specific sequence is identified ( Fig. 4, refs 213,221,222 ). Ligands isolated from the primary screen of one-bead-one-peptide libraries often have low to moderate activity.…”

Section: Tricks and Analytical Techniques For Evaluation Of One-bead-mentioning

confidence: 99%

See 1 more Smart Citation

Molecular Diversity and Libraries of Structures: Synthesis and Screening

Rinnová

Lebl²

1996

Collect. Czech. Chem. Commun.

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Library, or molecular diversity, approaches are a progressive tool in contemporary investigation of biological interactions and drug discovery. All library approaches include certain degree of rationality and cannot be therefore classified as random or irrational techniques. Reviewed techniques are complementary to so called "rational design"; they can serve either as a tool to generate a lead, or, on the other hand, to optimize a "designed" lead by rapid evaluation of structure-activity relationships. Combinatorial approaches are based on either a random or multiple principle which enables production of large number of diverse molecular structures that can be simultaneously screened and evaluated in a biological assay to find an optimal interacting molecule.

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Nonsequenceable and/or nonpeptide libraries

Cited by 11 publications

References 1 publication

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

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

One‐bead–one‐structure combinatorial libraries

Molecular Diversity and Libraries of Structures: Synthesis and Screening

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