Synthesis of Peptides Containing a Combination of Free and 2-trans-Cyclooctene Carbamate Protected Lysine Residues.

Autor: Doelman W; Leiden Institute of Chemistry, Leiden, the Netherlands., Ligthart NAM; Leiden Institute of Chemistry, Leiden, the Netherlands., van de Plassche MAT; Leiden Institute of Chemistry, Leiden, the Netherlands., de Geus MAR; Leiden Institute of Chemistry, Leiden, the Netherlands., Reinalda L; Leiden Institute of Chemistry, Leiden, the Netherlands., Isendoorn MME; Leiden Institute of Chemistry, Leiden, the Netherlands., Filippov DV; Leiden Institute of Chemistry, Leiden, the Netherlands., van Kasteren SI; Leiden Institute of Chemistry, Leiden, the Netherlands.
Jazyk: angličtina
Zdroj: Chembiochem : a European journal of chemical biology [Chembiochem] 2024 Feb 16; Vol. 25 (4), pp. e202300786. Date of Electronic Publication: 2024 Jan 17.
DOI: 10.1002/cbic.202300786
Abstrakt: The allylic trans-cyclooctene (TCO) functionality facilitates powerful control over the spatiotemporal activity of bio-active molecules, enabling precision targeting of druglike and imaging modalities. However, the introduction of this function onto molecules remains chemically challenging, particularly for peptides. Modification with TCOs of this important class of biomolecules remains a challenge, primarily due to the sensitivity of the TCO group to the strong acids typically used in global deprotection during solid phase peptide synthesis. Here, we present a novel synthetic approach to site-selectively introduce TCO-groups in peptides. Our approach utilizes azide groups to mask amine functions, enabling selective introduction of the TCO on a single lysine residue. Staudinger reduction of the azides back to the corresponding amines proceeds without disturbing the sensitive TCO. We show that using our method, we can produce TCO-inactivated antigenic peptides of previously unseen complexity.
(© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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