Solid-Phase Synthesis of Peptides Containing Aminoadipic Semialdehyde Moiety and Their Cyclisations

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

Abstract

Pathological levels of oxidative stress (OS) have been implicated in many diseases including diabetes mellitus, neurodegenerative diseases, infammatory 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 solidphase 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 confrmed the sequences of the modifed 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-tetrahydropyridine2-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
Author Monika Kijewska - University of Wrocław (UWr)
Monika Kijewska,,
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, Mateusz Waliczek - University of Wrocław (UWr)
Mateusz Waliczek,,
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, Marta Cal - University of Wrocław (UWr)
Marta Cal,,
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, Łukasz Jaremko - King Abdullah University of Science and Technology (KAUST)
Łukasz Jaremko,,
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, Mariusz Jaremko - King Abdullah University of Science and Technology (KAUST)
Mariusz Jaremko,,
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, Maria Król - University of Wrocław (UWr)
Maria Król,,
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, Marta Kołodziej (EaE / IChaFT / DAEaQA) - [inna]
Marta Kołodziej,,
- Department of Agricultural Engineering and Quality Analysis
- inna
, Marek Lisowski - University of Wrocław (UWr)
Marek Lisowski,,
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, Piotr Stefanowicz - University of Wrocław (UWr)
Piotr Stefanowicz,,
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, Zbigniew Szewczuk - University of Wrocław (UWr)
Zbigniew Szewczuk,,
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Journal seriesScientific Reports, ISSN 2045-2322, (A 40 pkt)
Issue year2018
Vol8
No1
Pages1-11
Publication size in sheets0.5
Article number10462
ASJC Classification1000 Multidisciplinary
DOIDOI:10.1038/s41598-018-28798-9
URL https://www.nature.com/articles/s41598-018-28798-9.pdf
Languageen angielski
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Kijewska_Waliczek_Cal_Jaremko_Krol_Kolodziej_Lisowski_Stefanowicz_Szewczuk_Solid_Phase_Synthesis_Of_Peptides.pdf 1,46 MB
Score (nominal)40
Score sourcejournalList
Publication indicators WoS Citations = 2; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.401; WoS Impact Factor: 2018 = 4.011 (2) - 2018=4.525 (5)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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