Enzymatic C‐to‐C Protein Ligation
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.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Enzymatic C‐to‐C Protein Ligation ; day:25 ; month:01 ; year:2022 ; extent:1
Angewandte Chemie / International edition. International edition ; (25.01.2022) (gesamt 1)
- Creator
- DOI
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10.1002/anie.202116672
- URN
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urn:nbn:de:101:1-2022012514143721920511
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:22 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Rehm, Fabian B. H.
- Tyler, Tristan J.
- de Veer, Simon J.
- Craik, David
- Durek, Thomas
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Enzymatic Fluoromethylation as a Tool for ATP‐Independent Ligation
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Diels-Alder ligation of peptides and proteins
Enzymatische Ligation von Peptiden, Peptidnucleinsäuren und Proteinen
Enzymatic C‐to‐C Protein Ligation
Template‐Directed Copying of RNA by Non‐enzymatic Ligation †
Enzymatic Fluoromethylation as a Tool for ATP‐Independent Ligation
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Enzymatic Fluoromethylation as a Tool for ATP‐Independent Ligation
Expressed Protein Selenoester Ligation
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Protein semisynthesis and engineering by expressed protein ligation
Protein trans- splicing as a protein ligation tool to study protein structure and function
Synthesis of artificial building blocks for sortase-mediated ligation and their enzymatic linkage
Diels-Alder ligation of peptides and proteins