Bildung und Umlagerung von Homoserin‐Depsipeptiden und ‐proteinen durch α‐Ketosäure‐Hydroxylamin‐Ligation mit 5‐Oxaprolin

Wucherpfennig, Thomas; Rohrbacher, Florian; Pattabiraman, Vijaya R.; Bode, Jeffrey W.

doi:10.1002/ange.201406097

Cited by 8 publications

(2 citation statements)

References 36 publications

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“…During studies in dipeptide model systems, it was found that ligations with 5-oxaproline give unexpectedly the depsipeptide with an ester linkage rather than the anticipated amide (Scheme 28, see also mechanism in the section "Type II") [26,27]. Conveniently, these depsipeptides are readily rearranged to the amides in basic buffers.…”

Section: Formation and Rearrangement Of Depsipeptidesmentioning

confidence: 96%

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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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Section: Formation and Rearrangement Of Depsipeptidesmentioning

confidence: 96%

“…Chemical Protein Synthesis with the KAHA Ligation reaction is the ester and not the expected amide [26,27]. Most likely, the alcoholwhich is released upon decarboxylation -can intercept the intermediate nitrilium in an intramolecular addition.…”

Section: Scheme 4 Mechanism For Type I Ligationsmentioning

confidence: 98%

Chemical Protein Synthesis with the KAHA Ligation

Rohrbacher

Wucherpfennig

Bode

2014

Topics in Current Chemistry

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Chemical Synthesis of the 20 kDa Heme Protein Nitrophorin 4 by α‐Ketoacid‐Hydroxylamine (KAHA) Ligation

Kulkarni

Thuaud

et al. 2015

Angewandte Chemie

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The chemical synthesis of the 184-residue ferric heme-binding protein nitrophorin 4w as accomplished by sequential couplings of five unprotected peptide segments using a-ketoacid-hydroxylamine (KAHA) ligation reactions. The fully assembled protein was folded to its native structure and coordinated to the ferric heme bc ofactor.T he synthetic holoprotein, despite four homoserine residues at the ligation sites,s howed identical properties to the wild-type protein in nitric oxide binding and nitrite dismutase reactivity.This work establishes the KAHA ligation as av aluable and viable approach for the chemical synthesis of proteins up to 20 kDa and demonstrates that it is well-suited for the preparation of hydrophobic protein targets.

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Eine Threonin‐bildende Oxazetidinaminosäure für die chemische Synthese von Proteinen mittels KAHA‐Ligation

2019

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Die Ligation von α‐Ketosäure‐Hydroxylamin (KAHA) erlaubt die chemoselektive Verknüpfung von ungeschützten Peptidsegmenten unter Bildung einer Amidbindung. Die zurzeit meistgenutzte Variante basiert auf einem fünfgliedrigen cyclischen Hydroxylamin, welches einen Homoserinester als Hauptligationsprodukt bildet. Ein neues viergliedriges cyclisches Hydroxylamin wurde synthetisiert, um die natürliche Aminosäure Threonin an der Ligationsstelle bildet. Dieses Monomer wurde für die Synthese der Proteine UbcH5a (146 Aminosäuren) und TI I27 (89 Aminosäuren) eingesetzt. Sowohl das so synthetisierte UbcH5a als auch die Variante, die unter Verwendung des fünfgliedrigen zyklischen Hydroxylamins synthetisiert wurde, zeigten identische Aktivitäten gegenüber der rekombinanten Variante in einem Ubiquitinierungs‐Assay.

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Bildung und Umlagerung von Homoserin‐Depsipeptiden und ‐proteinen durch α‐Ketosäure‐Hydroxylamin‐Ligation mit 5‐Oxaprolin

Cited by 8 publications

References 36 publications

Chemical Protein Synthesis with the KAHA Ligation

Chemical Protein Synthesis with the KAHA Ligation

Chemical Synthesis of the 20 kDa Heme Protein Nitrophorin 4 by α‐Ketoacid‐Hydroxylamine (KAHA) Ligation

Eine Threonin‐bildende Oxazetidinaminosäure für die chemische Synthese von Proteinen mittels KAHA‐Ligation

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