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SEA Ligation Is Accelerated at Mildly Acidic pH. Application to the Formation of Difficult Peptide Junctions

preprint
submitted on 19.12.2019 and posted on 23.12.2019 by Marine Cargoet, Vincent Diemer, Laurent Raibaut, Elizabeth Lissy, Benoît Snella, Vangelis Agouridas, Oleg Melnyk
The bis(2-sulfanylethyl)amido (SEA)-mediated ligation has been introduced in 2010 as a novel chemoselective peptide bond forming reaction. SEA ligation is a useful reaction for protein total synthesis that is complementary to the native chemical ligation (NCL). In particular, SEA ligation proceeds efficiently in a wide range of pH, from neutral pH to pH 3-4. Thus, the pH can be chosen to optimize the solubility of the peptide segments or final product. It can be also chosen to facilitate the formation of difficult junctions, since the rate of SEA ligation increases significantly by decreasing the pH from 7.2 to 4.0. Here we describe a protocol for SEA ligation at pH 5.5 in the presence of 4-mercaptophenylacetic acid (MPAA) or at pH 4.0 in the presence of a newly developed diselenol catalyst. The protocols describe the formation of a valyl-cysteinyl peptide bond between two model peptides.

History

Email Address of Submitting Author

oleg.melnyk@ibl.cnrs.fr

Institution

CNRS, Université de Lille, INSERM, Institut Pasteur de Lille

Country

France

ORCID For Submitting Author

0000-0002-3863-5613

Declaration of Conflict of Interest

The authors declare no conflict of interests

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