Chemoselectively addressable HCan building blocks in peptide synthesis:L-homocanaline derivatives

Lang, Irmtraud; Donzé, N.; Garrouste, Patrick; Dumy, Pascal; Mutter, Manfred

doi:10.1002/(sici)1099-1387(199802)4:1<72::aid-psc130>3.0.co;2-g

Cited by 14 publications

(5 citation statements)

References 20 publications

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“…This is in accordance with observations from other oxyamine amino acids used in peptide synthesis (e.g. homocanaline) [26].…”

supporting

confidence: 93%

“…In nature, the oxyamino side-chain functionality is found in the canaline amino acid (L-2-amino-4aminooxy-butyric acid) [24,25]. An oxyamine analogue of lysine, L-homocanaline, was recently prepared as the Fmoc/Boc-protected derivative through a seven-step synthesis [26]. We preferred the shortest possible side-chain in order to limit structural flexibility.…”

Section: Introductionmentioning

confidence: 99%

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Preparation and application ofO-amino-serine, Ams, a new building block in chemoselective ligation chemistry

Spetzler

Høeg-Jensen

1999

J. Peptide Sci.

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The non-codable amino acid O-amino-serine, Ams, has been prepared in both L- and D-forms as the orthogonally protected derivative, Fmoc-Ams(Boc)-OH (1 and 2). This new amino acid derivative is useful for chemoselective ligations. Under acidic conditions and in the presence of all other common amino acid functionalities, the oxyamine function selectively forms oxime linkages with aldehydes. The Ams residue has been incorporated into both ends of the peptide sequence Asp-Leu-Trp-Gln-Lys using standard SPPS. The deprotected peptide has been used for chemical ligation to afford a peptide dimer as well as a glycopeptide. Ams racemization was found to be negligible, as monitored by HPLC separation of Ams dipeptide diastereomers.

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“…This is in accordance with observations from other oxyamine amino acids used in peptide synthesis (e.g. homocanaline) [26].…”

supporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Preparation and application ofO-amino-serine, Ams, a new building block in chemoselective ligation chemistry

Spetzler

Høeg-Jensen

1999

J. Peptide Sci.

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“…The major components of the mixture were identified as methyl (Boc-Aoa) 5 -a-D-Galp and methyl (Boc-Aoa) 6 -a-D-Galp arising from N-acylation of the desired tetra-O-acyl template. The problem was obviously insufficient protection of the a-nucleophilic nitrogen in Boc-Aoa-OH, a problem previously noticed by Mutter and coworkers [60]. While they circumvented the problem using trityl-protected aminooxyacetic acid (TrtAoa-OH), we explored the possibility of attaching a second Boc group to the nitrogen in Boc-Aoa-OH.…”

Section: The Second Generationmentioning

confidence: 99%

Carbohydrates as templates for control of distance-geometry in de novo-designed proteins

Jensen¹,

Brask

2002

CMLS, Cell. Mol. Life Sci.

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An understanding of very complex natural systems can often only be achieved through detailed studies of systems with a reduced complexity. Thus, de novo design of proteins allows the study of fundamental forces determining protein folding and stability, as well as protein-protein interactions, by analyses of protein models of structural motifs. In addition, de novo design may lead to new biomimetic molecules with novel properties. In a synthetic approach to achieve structural economy, rigid templates, sometimes called topological scaffolds, have been used to connect secondary-structure elements, most notably alpha-helices. By positioning the helices on the template, the unfavorable entropy of protein folding is reduced. In a novel class of chimeric molecules called carboproteins, carbohydrates are used as templates for de novo design of protein models. Recently, a strategy relying on chemoselective ligation of C-terminal peptide aldehydes to tetra-aminooxy functionalized monosaccharides has provided 7-kDa 4-alpha-helix bundle carboproteins.

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“…Aminooxy-containing peptides are usually obtained by inserting the classical N -Boc-protected 2-(aminooxy)acetic acid (Aoa) at the last stage of peptide synthesis either at N -terminus or side-chain position. − Although not clearly delineated in the literature, − there was reported evidence that this constraint results from the high reactivity of the N -protected aminooxy function exhibited during peptide coupling condition. Indeed, significant N -overacylation was observed during the insertion of the Aoa building block which led to heterogeneous peptides.…”

Section: Introductionmentioning

confidence: 99%

1-Ethoxyethylidene, a New Group for the Stepwise SPPS of Aminooxyacetic Acid Containing Peptides

et al. 2008

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For more than a decade, the oxime ether ligation has proven to be one of the most efficient technique for the preparation of various peptide conjugates. However, despite numerous reports, the preparation of aminooxy-containing peptides is still hampered by N-overacylation of the NH-O function either during its incorporation or through the peptide-chain elongation. This restricts the introduction of protected-NH-O function at the last acylation step and prevents the use of standard solid-phase peptide synthesis (SPPS) procedures for the preparation of more complex aminooxy-peptides. We have studied the coupling of modified Fmoc-lysine containing either N-Boc- or N,N'-bis-Boc-protected aminooxyacetic acids (Aoa) during the elongation of the peptide chain and found that none of them is adequate. To circumvent this limitation, we propose to protect the Aoa moiety with a 1-ethoxyethylidene group (Eei) to provide 2-(1-ethoxyethylideneaminooxy)acetic acid building block. We showed that the Eei group is fully compatible with standard SPPS conditions and safely allows the multiple incorporation of the aminooxy functionality into the growing peptide. Since Eei-protected Aoa remains as flexible as normal amino acids in peptide synthesis, it may become the rule for the straightforward preparation of aminooxy peptides.

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Chemoselectively addressable HCan building blocks in peptide synthesis:L-homocanaline derivatives

Cited by 14 publications

References 20 publications

Preparation and application ofO-amino-serine, Ams, a new building block in chemoselective ligation chemistry

Preparation and application ofO-amino-serine, Ams, a new building block in chemoselective ligation chemistry

Carbohydrates as templates for control of distance-geometry in de novo-designed proteins

1-Ethoxyethylidene, a New Group for the Stepwise SPPS of Aminooxyacetic Acid Containing Peptides

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