Asparagine as a masked dehydroalanine residue in solid phase peptide synthesis

Blettner, Carsten G.; Bradley, Mark

doi:10.1016/0040-4039(94)85082-8

Cited by 17 publications

(13 citation statements)

References 15 publications

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“…Such a strategy would preferably require the nitrogen of the amine to be part of the bond which is broken during cleavage from the resin. We concluded that the classical Hofmann elimination reaction would serve our purposes well. , The reaction is usually considered to be a useful method for the synthesis of alkenes and indeed had previously been used by Bradley and co-workers to synthesize dehydroalanine derivatives on a resin . It became apparent that we could achieve our objective of releasing a tertiary amine into solution while the alkene component remained resin-bound.…”

mentioning

confidence: 82%

Synthesis of Tertiary Amines Using a Polystyrene (REM) Resin

Brown¹,

Rees²,

Rankovic³

et al. 1997

J. Am. Chem. Soc.

120

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A range of tertiary amines was constructed using a “traceless” linker on a polystyrene resin (REM resin), starting from secondary amines, primary amines, and resin-bound “ammonia”. The methodology is characterized by three essential steps conducted under ambient conditions: (1) coupling of the starting amine (Michael addition) to the resin, (2) activation (quaternization), and (3) cleavage of the product amine (Hofmann elimination). The linker is compatible with both acid and base sensitive protecting group strategies. The nature of the chemistry ensures that the tertiary amine products are obtained in consistently high purity (95% or greater). After cleavage of the product, REM resin is regenerated and can be reused for repeat syntheses. The yield and purity of repeat batches is maintained over 5 cycles, allowing the automated synthesis of >0.5 g quantities of pure tertiary amine.

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mentioning

confidence: 82%

Synthesis of Tertiary Amines Using a Polystyrene (REM) Resin

Brown¹,

Rees²,

Rankovic³

et al. 1997

J. Am. Chem. Soc.

120

View full text Add to dashboard Cite

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“…The α, β-unsaturated amino acid, dehydroalanine, is often found in biological polypeptides and natural products [135,136], and from a synthetic point of view represents a useful electrophilic precursor for preparation of peptide conjugates such as glycopeptides and lipopeptides. Introduction of dehydroamino acid can be achieved by various methodologies [137] with the most common ones being the activation and elimination of serine residues or Hoffmann elimination of 2,3-diaminopropionic acid [138]. These methods might be useful for specific peptides, but lack overall sufficient chemoselectivity.…”

Section: Dehydroamino Acids -Versatile Precursorsmentioning

confidence: 99%

Selenopeptide chemistry

Muttenthaler¹,

Alewood²

2008

Journal of Peptide Science

143

149

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This review focuses on the chemical aspects of the 21st proteinogenic amino acid, selenocysteine in peptides and proteins. It describes the physicochemical properties of selenium/sulfur and selenocysteine/cysteine based on comprehensive structural (X-ray, NMR, CD) and biological data, and illustrates why selenocysteine is considered the most conservative substitution of cysteine. The main focus lies on the synthetic methods on selenocysteine incorporation into peptides and proteins, including an overview of the selenocysteine building block syntheses for Boc- and Fmoc-SPPS. Selenocysteine-mediated reactions such as native chemical ligation and dehydroalanine formation are addressed towards peptide conjugation. Selenopeptides have very interesting and distinct properties which lead to a diverse range of applications such as structural, functional and mechanistic probes, robust scaffolds, enzymatic reaction design, peptide conjugations and folding tools.

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“…After removal of Fmoc group with 20% Pip/DMF, Fmoc protected ( S )- or ( R )-Asn-OH was activated for coupling with ( S )- or ( R )-Fmoc-Asn-OH in the presence of DCC/HOBt. The Hofmann rearrangement of the primary amide of Asn into the corresponding amine was performed on resin using PhI(OCOCF 3 ) 2 (PIFA) and pyridine in DMF/H 2 O [ 45 ]. The resulting Nα-Fmoc-Dap residue was coupled at the β-amino group with MPUPA under the same conditions described above.…”

Section: Resultsmentioning

confidence: 99%

Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured Materials

et al. 2021

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Arg-Gly-Asp (RGD)-binding integrins, e.g., αvβ3, αvβ1, αvβ5 integrins, are currently regarded as privileged targets for the delivery of diagnostic and theranostic agents, especially in cancer treatment. In contrast, scarce attention has been paid so far to the diagnostic opportunities promised by integrins that recognize other peptide motifs. In particular, α4β1 integrin is involved in inflammatory, allergic, and autoimmune diseases, therefore, it represents an interesting therapeutic target. Aiming at obtaining simple, highly stable ligands of α4β1 integrin, we designed hybrid α/β peptidomimetics carrying linkable side chains for the expedient functionalization of biomaterials, nano- and microparticles. We identified the prototypic ligands MPUPA-(R)-isoAsp(NHPr)-Gly-OH (12) and MPUPA-Dap(Ac)-Gly-OH (13) (MPUPA, methylphenylureaphenylacetic acid; Dap, 2,3-diamino propionic acid). Modification of 12 and 13 by introduction of flexible linkers at isoAsp or Dap gave 49 and 50, respectively, which allowed for coating with monolayers (ML) of flat zeolite crystals. The resulting peptide–zeolite MLs were able to capture selectively α4β1 integrin-expressing cells. In perspective, the α4β1 integrin ligands identified in this study can find applications for preparing biofunctionalized surfaces and diagnostic devices to control the progression of α4β1 integrin-correlated diseases.

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Asparagine as a masked dehydroalanine residue in solid phase peptide synthesis

Cited by 17 publications

References 15 publications

Synthesis of Tertiary Amines Using a Polystyrene (REM) Resin

Synthesis of Tertiary Amines Using a Polystyrene (REM) Resin

Selenopeptide chemistry

Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured Materials

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