Synthesis of Nε‐acetyl‐L‐homolysine by the Lossen rearrangement and its application for probing deacetylases and binding modules of acetyl‐lysine. (19th December 2022)

• Record Type: Journal Article
• Authors: Rehkopf, Luisa; Seidel, Julian; Sindlinger, Julia; Wang, Mary; Kirchgäßner, Sören; Schwarzer, Dirk
• Is Part Of: Journal of peptide science. Volume 29:Number 4(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-19
• Subjects: bromodomains -- homolysine -- lysine acetylation -- peptide probes -- sirtuins; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.3462
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : Lysine acetylation is a posttranslational protein modification mediating protein–protein interactions by recruitment of bromodomains. Investigations of bromodomains have focused so far on the sequence context of the modification site and acyl‐modifications installed at lysine side chains. In contrast, there is only little information about the impact of the lysine residue that carries the modification on bromodomain binding. Here, we report a synthesis strategy for L‐acetyl‐homolysine from L‐2‐aminosuberic acid by the Lossen rearrangement. Peptide probes containing acetylated homolysine, lysine, and ornithine were generated and used for probing the binding preferences of four bromodomains from three different families. Tested bromodomains showed distinct binding patterns, and one of them bound acetylated homolysine with similar efficiency as the native substrate containing acetyl‐lysine. Deacetylation assays with a bacterial sirtuin showed a strong preference for acetylated lysine, despite a broad specificity for N‐acyl modifications. Abstract : A synthesis strategy for L‐acetyl‐homolysine from L‐2‐aminosuberic acid by the Lossen rearrangement is reported. Peptide probes containing acetylated homolysine, lysine, and ornithine were used to define the binding preferences of four bromodomains from three different families. One of the bromodomains bound acetylated homolysine with similar efficiency as the native substrate containing acetyl‐lysine.