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]
![]() |
PDF
1MB |
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: |
| ||||||
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 |
Repository Staff Only: item control page