Insight into the SEA amide thioester equilibrium. Application to the synthesis of thioesters at neutral pH.
The bis(2-sulfanylethyl)amide (SEA) N,S-acyl shift thioester surrogate has found a variety of useful applications in the field of protein total synthesis. Here we present novel insights into the SEA amide/thioester equilibrium in water which is an essential step in any reaction involving the thioester surrogate properties of the SEA group. We also show that the SEA amide thioester equilibrium can be efficiently displaced at neutral pH for accessing peptide alkylthioesters, i.e. the key components of the native chemical ligation (NCL) reaction.
Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France. oleg.melnyk@ibl.cnrs.fr.
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Pira
Université Sidi Mohamed Ben Abdellah, Morocco.
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El Mahdi
Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France. oleg.melnyk@ibl.cnrs.fr.
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Raibaut
Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France. oleg.melnyk@ibl.cnrs.fr.
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Drobecq
Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France. oleg.melnyk@ibl.cnrs.fr.
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Dheur
Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France. oleg.melnyk@ibl.cnrs.fr.
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Boll
Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161 - M3T - Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France. oleg.melnyk@ibl.cnrs.fr.
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Melnyk