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A Straightforward Methodology to Overcome Solubility Challenges for N-Terminal Cysteinyl Peptide Segments Used in Native Chemical Ligation

preprint
submitted on 01.11.2020, 22:21 and posted on 03.11.2020, 06:39 by Skander Abboud, El hadji Cisse, Michel Doudeau, Hélène Bénédetti, Vincent AUCAGNE
One of the main limitations encountered during the chemical synthesis of proteins through native chemical ligation (NCL) is the limited solubility of some of the peptide segments. The most commonly used solution to overcome this problem is to derivatize the segment with a temporary solubilizing tag. Conveniently, the tag can be introduced on the thioester segment in such a way that it is removed concomitantly with the NCL reaction. We herein describe a generalization of this approach to N-terminal cysteinyl segment counterparts, using a straightforward synthetic approach that can be easily automated from commercially available building blocks, and applied it to a well-known problematic target, SUMO-2 (93 amino acids).

Funding

ANR (EasyMiniprot, ANR-15-CE07-0022)

History

Email Address of Submitting Author

aucagne@cnrs-orleans.fr

Institution

CNRS - Centre de Biophysique Moléculaire (UPR4301)

Country

France

ORCID For Submitting Author

0000-0002-2647-0188

Declaration of Conflict of Interest

No conflict of interest to declare.

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