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In-peptide amino acid racemization via inter-residue oxazoline intermediates during acidic hydrolysis

Broberg, Anders and Nord, Christina and Levenfors, Jolanta and Bjerketorp, Joakim and Guss, Bengt and Öberg, Bo (2021). In-peptide amino acid racemization via inter-residue oxazoline intermediates during acidic hydrolysis. Amino Acids. 53 , 323-331
[Research article]

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Abstract

Isopedopeptins are antibiotic cyclic lipodepsipeptides containing the subsequence L-Thr-L-2,3-diaminopropanoic acid-D-Phe-L-Val/L-3-hydroxyvaline. Acidic hydrolysis of isopedopeptins in D2O showed the D-Phe residues to racemize extensively in peptides with L-3-hydroxyvaline but not in peptides with L-Val. Similarly, one Leu residue in pedopeptins, which are related peptides containing the subsequence Leu-2,3-diaminopropanoic acid-Leu-L-Val/L-3-hydroxyvaline, was found to racemize in peptides with L-3-hydroxyvaline. Model tetrapeptides, L-Ala-L-Phe-L-Val/3-hydroxyvaline-L-Ala, gave the corresponding results, i.e. racemization of L-Phe only when linked to a L-3-hydroxyvaline. We propose the racemization to proceed via an oxazoline intermediate involving Phe/Leu and the L-3-hydroxyvaline residues. The 3-hydroxyvaline residue may form a stable tertiary carbocation by loss of the sidechain hydroxyl group as water after protonation. Elimination of the Phe/Leu H-2 and ring-closure from the carbonyl oxygen onto the carbocation results in the suggested oxazoline intermediate. The reversed reaction leads to either retained or inversed configuration of Phe/Leu. Such racemization during acidic hydrolysis may occur whenever a 3-hydroxyvaline residue or any amino acid that can form a stable carbocation on the C-3, is present in a peptide. The proposed mechanism for racemization was supported by incorporation of O-18 in the 3-hydroxyvaline sidechain when the acidic hydrolysis was performed in H2O/(H2O)-O-18 (1:1). The 2,3-diaminopropanoic residues of isopedopeptins and pedopeptins were also found to racemize during acidic hydrolysis, as previously described. Based on the results, the configuration of the Leu and 2,3-diaminopropanoic acid residues of the pedopeptins were reassigned to be L-Leu and D-Leu, and 2 x L-2,3-diaminopropanoic acid.

Authors/Creators:Broberg, Anders and Nord, Christina and Levenfors, Jolanta and Bjerketorp, Joakim and Guss, Bengt and Öberg, Bo
Title:In-peptide amino acid racemization via inter-residue oxazoline intermediates during acidic hydrolysis
Series Name/Journal:Amino Acids
Year of publishing :2021
Volume:53
Page range:323-331
Number of Pages:9
Publisher:SPRINGER WIEN
ISSN:0939-4451
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Biochemistry and Molecular Biology
Keywords:Peptide hydrolysis, Racemization of amino acids, Oxazoline, 3-hydroxyvaline, Pedobacter cryoconitis
URN:NBN:urn:nbn:se:slu:epsilon-p-111010
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-111010
Additional ID:
Type of IDID
DOI10.1007/s00726-021-02951-7
Web of Science (WoS)000617850200001
ID Code:22964
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
VH - Faculty of Veterinary Medicine and Animal Science
Department:(NL, NJ) > Department of Molecular Sciences
(VH) > Department of Biomedical Science and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:07 Apr 2021 09:23
Metadata Last Modified:07 Apr 2021 09:31

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