Protecting Groups in Solid-Phase Organic Synthesis

Orain, David; Ellard, John; Bradley, Mark

doi:10.1021/cc0001093

Cited by 53 publications

(34 citation statements)

References 115 publications

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“…of Fmoc‐OSu to generate similar outer layer as the initial step. At this time, we purposely used Alloc‐OSu to protect all the N‐terminal amino groups in the bead interior, because Alloc‐group can be removed later with palladium in the presence of Fmoc‐ and Boc‐groups (14–16). Upon Fmoc‐deprotection, p‐Nle‐D‐I motif was assembled onto the random tetrapeptide segment on the outer layer of the bead with Fmoc‐chemistry while the bead interior was Alloc‐protected.…”

Section: Generation Of Motif‐based Secondary Librariesmentioning

confidence: 99%

Applications of topologically segregated bilayer beads in ‘one‐bead one‐compound’ combinatorial libraries

Wang

Liu

et al. 2005

The Journal of Peptide Research

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We recently reported the use of a biphasic approach to generate topologically segregated bilayer beads. In generating 'one-bead one-compound' (OBOC) combinatorial libraries, novel encoding methods have been applied to these beads such as the testing library compound and the coding tags residing on the outer layer and inner core of each bead, respectively. In this report, we further exploit these bilayer beads by preparing target bead-libraries with low concentration of random peptides on the outer layer, and full substitution of coding peptides in the bead interior. The low concentration of peptide on the bead surface enables us to greatly increase the stringency of screening so that higher affinity ligands can easily be identified. Full substitution of the inner core of the beads enables us to have enough coding peptides inside the bead for direct microsequencing with Edman chemistry. The biphasic approach of preparing bilayer beads can be carried out at any point during the library construction. Therefore, the nonsequencable or fixed structures of the peptides can be bypassed in the coding tags. As a result, peptide libraries that otherwise cannot be sequenced can now be sequenced, and peptide segments with fixed residues within the libraries can be bypassed so that the microsequencing time can be significantly shortened. Furthermore, peptides with a branch of random sequence in the middle of a fixed peptide chain can be encoded with just the random sequence in the bead interior. We have successfully applied these novel OBOC library concepts in the optimization of cell-surface ligands for a human T-cell leukemia, Jurkat, cell line.

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Section: Generation Of Motif‐based Secondary Librariesmentioning

confidence: 99%

Applications of topologically segregated bilayer beads in ‘one‐bead one‐compound’ combinatorial libraries

Wang

Liu

et al. 2005

The Journal of Peptide Research

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“…In addition to the cyclic and linear scaffold designs with three different orthogonal deprotecting groups, similar type of scaffolds were designed with a fourth orthogonal protecting group, an allyloxycarbonyl (Alloc) protecting group that was removed using an Alloc deprotecting solution similar to the work of Orain et al [37]. This scaffold was used to produce a linear peptide with every combination of four carboxylic acid groups from a set of seven different carboxylic acid groups (including the DNP and 4-ethoxyphenylacetic acid) in addition to sequences containing the two controls, biotin as the positive control and acetic anhydride as the negative control.…”

Section: Application Of Quantum Dots and Longer Scaffolds On Doc-pmentioning

confidence: 99%

Construction and Evaluation of an Automated Light Directed Protein-Detecting Microarray Synthesizer

Marthandan¹,

Klyza

et al. 2008

IEEE Trans.on Nanobioscience

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We have designed, constructed, and evaluated an automated instrument that has produced high-density arrays with more than 30 000 peptide features within a 1.5 cm(2) area of a glass slide surface. These arrays can be used for high throughput library screening for protein binding ligands, for potential drug candidate molecules, or for discovering biomarkers. The device consists of a novel fluidics system, a relay control electrical system, an optics system that implements Texas Instruments' digital micromirror device (DMD), and a microwave source for accelerated synthesis of peptide arrays. The instrument implements two novel solid phase chemical synthesis strategies for producing peptide and peptoid arrays. Biotin-streptavidin and DNP anti-DNP (dinitrophenol) models of antibody small molecule interactions were used to demonstrate and evaluate the instrument's capability to produce high-density protein detecting arrays. Several screening assay and detection schemes were explored with various levels of efficiency and assays with sensitivity of 10 nM were also possible.

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“…The linker 2 was attached to an acid labile trityl polystyrene resin and spacer and loaded with either Fmoc-phenylalanine or Fmoc-βalanine. Hereafter different cleavage mixtures which have previously been reported to remove the fluorenylmethyloxycarbonyl group were added [27], including DBU [28,29], DBU/HOBT [30,31], TBAF [32] and employing various concentrations of piperidine, with different solvents and reaction times. After acetylation (10% Ac 2 O in DMF) the trityl linker was cleaved from the resin and the amount of Fmoc-removal and cleavage of amino acid from the linker were estimated using HPLC.…”

Section: Fmoc-removal Studiesmentioning

confidence: 99%

A safety catch linker for Fmoc-based assembly of constrained cyclic peptides

2005

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Abstract:A new safety-catch linker for Fmoc solid-phase peptide synthesis of cyclic peptides is reported. The linear precursors were assembled on a tert-butyl protected catechol derivative using optimized conditions for Fmoc-removal. After activation of the linker using TFA, neutralization of the N -terminal amine induced cyclization with concomitant cleavage from the resin yielding the cyclic peptides in DMF solution. Several constrained cyclic peptides were synthesized in excellent yields and purities.

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Protecting Groups in Solid-Phase Organic Synthesis

Cited by 53 publications

References 115 publications

Applications of topologically segregated bilayer beads in ‘one‐bead one‐compound’ combinatorial libraries

Applications of topologically segregated bilayer beads in ‘one‐bead one‐compound’ combinatorial libraries

Construction and Evaluation of an Automated Light Directed Protein-Detecting Microarray Synthesizer

A safety catch linker for Fmoc-based assembly of constrained cyclic peptides

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