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Enzymatic C-to-C Protein Ligation.
- Source :
-
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2022 Mar 07; Vol. 61 (11), pp. e202116672. Date of Electronic Publication: 2022 Jan 25. - Publication Year :
- 2022
-
Abstract
- Transpeptidase-catalyzed protein and peptide modifications have been widely utilized for generating conjugates of interest for biological investigation or therapeutic applications. However, all known transpeptidases are constrained to ligating in the N-to-C orientation, limiting the scope of attainable products. Here, we report that an engineered asparaginyl ligase accepts diverse incoming nucleophile substrate mimetics, particularly when a means of selectively quenching the reactivity of byproducts released from the recognition sequence is employed. In addition to directly catalyzing formation of l-/d- or α-/β-amino acid junctions, we find C-terminal Leu-ethylenediamine (Leu-Eda) motifs to be bona fide mimetics of native N-terminal Gly-Leu sequences. Appending a C-terminal Leu-Eda to synthetic peptides or, via an intein-splicing approach, to recombinant proteins enables direct transpeptidase-catalyzed C-to-C ligations. This work significantly expands the synthetic scope of enzyme-catalyzed protein transpeptidation reactions.<br /> (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 1521-3773
- Volume :
- 61
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Angewandte Chemie (International ed. in English)
- Publication Type :
- Academic Journal
- Accession number :
- 35018698
- Full Text :
- https://doi.org/10.1002/anie.202116672