Accelerated microfluidic native chemical ligation at difficult amino acids toward cyclic peptides

[en] Cyclic peptide-based therapeutics have a promising growth forecast that justifies the development of microfluidic systems dedicated to their production, in phase with the actual transitioning toward continuous flow and microfluidic technologies for pharmaceutical production. The application of the most popular method for peptide cyclization in water, i.e., native chemical ligation, under microfluidic conditions is still unexplored. Herein, we report a general strategy for fast and efficient peptide cyclization using native chemical ligation under homogeneous microfluidic conditions. The strategy relies on a multistep sequence that concatenates the formation of highly reactive S-(2-((2-sulfanylethyl)amino)ethyl) peptidyl thioesters from stable peptide amide precursors with an intramolecular ligation step. With very fast ligation rates (<5 min), even for the most difficult junctions (including threonine, valine, isoleucine, or proline), this technology opens the door toward the scale-independent, expedient preparation of bioactive macrocyclic peptides.

Disciplines :

Chemistry

Author, co-author :

Ollivier, Nathalie ^✱

Toupy, Thomas ^✱; Université de Liège - ULiège > Département de chimie (sciences) > CITOS

Hartkoorn, Ruben

Desmet, Rémi

Monbaliu, Jean-Christophe ^✱; Université de Liège - ULiège > Département de chimie (sciences) > CITOS

Melnyk, Oleg ^✱

^✱ These authors have contributed equally to this work.

Language :

English

Title :

Accelerated microfluidic native chemical ligation at difficult amino acids toward cyclic peptides

Publication date :

2018

Journal title :

Nature Communications

eISSN :

2041-1723

Publisher :

Nature Publishing Group, United Kingdom

Volume :

Pages :

2847

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.nature.com/articles/s41467-018-05264-8#article-info

Available on ORBi :

since 23 July 2018

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