Solid-phase synthesis of peptides containing aminoadipic semialdehyde moiety and their cyclisations

Monika Kijewska, Mateusz Waliczek, Marta Cal, Lukasz Jaremko, Mariusz Jaremko, Maria Król, Marta Kołodziej, Marek Lisowski, Piotr Stefanowicz, Zbigniew Szewczuk

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Pathological levels of oxidative stress (OS) have been implicated in many diseases including diabetes mellitus, neurodegenerative diseases, inflammatory diseases, atherosclerosis, and cancer. Studies of oxidative stress are however complicated by the low concentration of oxidation products. To resolve this problem, we tested a new derivative of aminoadipic semialdehyde (Fmoc-Aea-OH) in the solid-phase synthesis of carbonylated peptides. We prepared a series of peptides with free and acetylated N-terminal amino groups using the Fmoc-Aea-OH reagent. LC-MS, ESI-MS, and MS/MS spectra confirmed the sequences of the modified peptides, although the LC-MS and ESI-MS spectra were dominated by signals corresponding to dehydration products. NMR studies of acetylated products revealed that the dominant product formed in this reaction contains a 1,2,3,4-tetrahydropyridine-2-carboxylic acid residue. Another side reaction in this system was the cleavage of the amide bond between the Aea residue and the amino acid moiety preceding it resulting in the formation of a side product with a six-membered ring at the N-terminus (2,3,4,5-tetrahydropyridine-2-carboxylic acid residue). We found that, depending on the peptide sequence, one of those side products is predominant. Our work suggests new methods for the solid-state synthesis of peptides containing unnatural amino acids.
Original languageEnglish (US)
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Jul 11 2018

Bibliographical note

KAUST Repository Item: Exported on 2021-02-19
Acknowledgements: This work was supported by a grant No UMO-2012/07/D/ST5/002324 from the Polish National Science Centre. M. J. and Ł. J would like to like to thank King Abdullah University of Science and Technology (KAUST) for financial support.

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