Solid-Phase Synthesis and Biological Evaluation of Peptides ADP-Ribosylated at Histidine.

Autor: Minnee H; Bio-Organic Synthesis Leiden Institute of Chemistry Leiden University RA-2300 Leiden The Netherlands., Rack JGM; Sir William Dunn School of Pathology University of Oxford South Parks Road Oxford OX1 3RE UK.; Current address: Medical Research Council Centre for Medical Mycology at the University of Exeter University of Exeter, Geoffrey Pope Building Stocker Road Exeter EX4 4QD UK., van der Marel GA; Bio-Organic Synthesis Leiden Institute of Chemistry Leiden University RA-2300 Leiden The Netherlands., Overkleeft HS; Bio-Organic Synthesis Leiden Institute of Chemistry Leiden University RA-2300 Leiden The Netherlands., Codée JDC; Bio-Organic Synthesis Leiden Institute of Chemistry Leiden University RA-2300 Leiden The Netherlands., Ahel I; Sir William Dunn School of Pathology University of Oxford South Parks Road Oxford OX1 3RE UK., Filippov DV; Bio-Organic Synthesis Leiden Institute of Chemistry Leiden University RA-2300 Leiden The Netherlands.
Jazyk: angličtina
Zdroj: Angewandte Chemie (Weinheim an der Bergstrasse, Germany) [Angew Chem Weinheim Bergstr Ger] 2024 Jan 22; Vol. 136 (4), pp. e202313317. Date of Electronic Publication: 2023 Nov 14.
DOI: 10.1002/ange.202313317
Abstrakt: The transfer of an adenosine diphosphate (ADP) ribose moiety to a nucleophilic side chain by consumption of nicotinamide adenine dinucleotide is referred to as ADP-ribosylation, which allows for the spatiotemporal regulation of vital processes such as apoptosis and DNA repair. Recent mass-spectrometry based analyses of the "ADP-ribosylome" have identified histidine as ADP-ribose acceptor site. In order to study this modification, a fully synthetic strategy towards α-configured N(τ)- and N(π)-ADP-ribosylated histidine-containing peptides has been developed. Ribofuranosylated histidine building blocks were obtained via Mukaiyama-type glycosylation and the building blocks were integrated into an ADP-ribosylome derived peptide sequence using fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase peptide synthesis. On-resin installation of the ADP moiety was achieved using phosphoramidite chemistry, and global deprotection provided the desired ADP-ribosylated oligopeptides. The stability under various chemical conditions and resistance against (ADP-ribosyl) hydrolase-mediated degradation has been investigated to reveal that the constructs are stable under various chemical conditions and non-degradable by any of the known ADP-ribosylhydrolases.
Competing Interests: The authors declare no conflict of interest.
(© 2023 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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