Synthesis of ‘difficult’ peptide sequences: application of a depsipeptide technique to the Jung–Redemann 10- and 26-mers and the amyloid peptide Aβ(1–42)

Carpino, Louis A.; Krause, Eberhard; Sferdean, Calin Dan; Schümann, Michael; Fabian, Heinz; Bienert, Michael; Beyermann, Michael

doi:10.1016/j.tetlet.2004.07.162

Cited by 181 publications

(138 citation statements)

References 15 publications

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“…47) This suggests that only one insertion of the isopeptide structure into the 42-residue peptide can suppress the aggregation nature of the peptide. On a relevant note, the O-acyl isopeptide possessed inhibitory activity against the aggregation of native Aβ1-42.…”

Section: O-acyl Isopeptide Of Aβ1-42mentioning

confidence: 99%

Medicinal Chemistry Focusing on Aggregation of Amyloid-β

Sohma

2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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The aggregation of peptides/proteins is intimately related to a number of human diseases. More than 20 have been identified which aggregate into fibrils containing extensive β-sheet structures, and species generated in the aggregation processes (i.e., oligomers and fibrils) contribute to disease development. Amyloid-β peptide (designated Aβ), related to Alzheimer's disease (AD), is the representative example. The intensive aggregation property of Aβ also leads to difficulty in its synthesis. To improve the synthetic problem, we developed an O-acyl isopeptide of Aβ1-42, in which the N-acyl linkage (amide bond) of Ser 26 was replaced with an O-acyl linkage (ester bond) at the side chain. The O-acyl isopeptide demonstrated markedly higher watersolubility than that of Aβ1-42, while it quickly converted to intact monomer Aβ1-42 via an O-to-N acyl rearrangement under physiological conditions. Inhibition of the pathogenic aggregation of Aβ1-42 might be a therapeutic strategy for curing AD. We succeeded in the rational design and identification of a small molecule aggregation inhibitor based on a pharmacophore motif obtained from cyclo[-Lys-Leu-Val-Phe-Phe-]. Moreover, the inhibition of Aβ aggregation was achieved via oxygenation (i.e., incorporation of oxygen atoms to Aβ) using an artificial catalyst. We identified a selective, cell-compatible photo-oxygenation catalyst of Aβ, a flavin catalyst attached to an Aβ-binding peptide, which markedly decreased the aggregation potency and neurotoxicity of Aβ.

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Section: O-acyl Isopeptide Of Aβ1-42mentioning

confidence: 99%

Medicinal Chemistry Focusing on Aggregation of Amyloid-β

Sohma

2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…This method, also named the depsipeptide method, has been successfully applied in the synthesis of difficult sequences [145][146][147][148]. Based on previous work on the synthesis of the more soluble o-acyl prodrug analogs [149,150], this technique involves the assembly of the O-acyl isopeptide and its later conversion to its peptide counterpart under physiological conditions (Scheme 2.4).…”

Section: O-acyl Isopeptidementioning

confidence: 99%

Methods for the Peptide Synthesis and Analysis

Tulla‐Puche

El‐Faham

Galanis

et al. 2015

Peptide Chemistry and Drug Design

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“…Conveniently, these depsipeptides are readily rearranged to the amides in basic buffers. They might also offer an advantage in terms of handling, as Scheme 27 Synthesis of GLP-1 F. Rohrbacher et al depsipeptides are in general more polar and more soluble than their amide counterparts [53].…”

Section: Formation and Rearrangement Of Depsipeptidesmentioning

confidence: 99%

Chemical Protein Synthesis with the KAHA Ligation

Rohrbacher

Wucherpfennig

Bode

2014

Topics in Current Chemistry

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Since the first report of the chemoselective amide bond forming reaction between α-ketoacids and hydroxylamines in 2006, the KAHA (α-ketoacid-hydroxylamine) ligation has advanced to a useful tool for the routine synthesis of small to medium sized proteins and cyclic peptides. In this chapter we introduce the concept of KAHA ligation starting with the synthesis and properties of hydroxylamines and α-ketoacids, methods for their incorporation into peptides, and give an insight into the mechanism of the KAHA ligation. We cover important improvements including sequential ligations with 5-oxaproline, traceless synthesis of peptide α-ketoacids and show their application in chemical protein synthesis and cyclic peptide synthesis. Recent developments of the KAT (potassium acyl trifluoroborate) ligation and its application as fast and chemoselective bioconjugation method are described and an outlook on ongoing work and possible future developments is given at the end of the chapter.

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Synthesis of ‘difficult’ peptide sequences: application of a depsipeptide technique to the Jung–Redemann 10- and 26-mers and the amyloid peptide Aβ(1–42)

Cited by 181 publications

References 15 publications

Medicinal Chemistry Focusing on Aggregation of Amyloid-β

Medicinal Chemistry Focusing on Aggregation of Amyloid-β

Methods for the Peptide Synthesis and Analysis

Chemical Protein Synthesis with the KAHA Ligation

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