Generation of antibody–drug conjugates by proximity-driven acyl transfer and sortase-mediated ligation DOI
Zhihui Cui, Hua Zhang,

Feng-Hao Zheng

et al.

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

We report a sortase-based site-specific antibody–drug conjugation strategy involving an affinity peptide-directed acyl transfer reaction and the sortase-mediated peptide ligation that allows for attachment of protein-based payloads to antibodies.

Language: Английский

Employing Broad Substrate Specificity of Omniligase to Generate Phage-Encoded Bicyclic Peptide Libraries for Ligand Discovery DOI

Xiao-Cui Wan,

Wenjing Zhu,

Huimin Wei

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

We report an enzymatic cyclization strategy termed omniligase-mediated peptide bicyclization. An electrophilic group was introduced into the recognition sequence of omniligase to achieve intramolecular bicyclization with Cys residues. In combination phage display, we identified a bicyclic ligand targeting TEAD4 KD value 1.5 μM, 100-fold lower than its linear version, demonstrating utility this platform for discovering ligands.

Language: Английский

Citations

0
Helicity‐Dependent Enzymatic Peptide Cyclization DOI Creative Commons

Canan Durukan,

Jannik Faierson,

Isabel van der Wal

et al.

Journal of Peptide Science, Journal Year: 2025, Volume and Issue: 31(6)

Published: April 27, 2025

ABSTRACT The secondary structure plays a crucial role in the biological activity of peptides. Various strategies have been developed to stabilize particular peptide conformations, including sequence modifications and macrocyclization approaches. Often, interplay between conformational constraint flexibility is central bioactivity. Here, we investigate how α‐helicity influences enzymatic head‐to‐tail cyclization using an engineered Sortase. We show that peptides with low helicity readily undergo intramolecular cyclization, while more rigid, helical exhibit complex behaviors cyclic dimer formation. These findings reveal increased rigidity can redirect reactions from intermolecular processes, demonstrates changes molecular guide chemical reactivity. insights advance design peptide‐derived materials, hydrogels, stimuli‐responsive probes.

Language: Английский

Citations

0
Generation of antibody–drug conjugates by proximity-driven acyl transfer and sortase-mediated ligation DOI
Zhihui Cui, Hua Zhang,

Feng-Hao Zheng

et al.

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

We report a sortase-based site-specific antibody–drug conjugation strategy involving an affinity peptide-directed acyl transfer reaction and the sortase-mediated peptide ligation that allows for attachment of protein-based payloads to antibodies.

Language: Английский

Citations

0