In-peptide amino acid racemization via inter-residue oxazoline intermediates during acidic hydrolysis
| Autor: | Bengt Guss, Christina Nord, Anders Broberg, Joakim Bjerketorp, Jolanta J. Levenfors, Bo Öberg |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
3-hydroxyvaline
Stereochemistry Clinical Biochemistry Peptide Protonation Oxazoline Carbocation 010402 general chemistry 01 natural sciences Biochemistry Peptides Cyclic Hydrolysis chemistry.chemical_compound Residue (chemistry) Isomerism Amino Acids Racemization Oxazoles chemistry.chemical_classification Organisk kemi 010405 organic chemistry Chemistry Racemization of amino acids Pedobacter cryoconitis Organic Chemistry Biochemistry and Molecular Biology Valine Dipeptides 0104 chemical sciences Amino acid Original Article Peptides Peptide hydrolysis Biokemi och molekylärbiologi |
| Zdroj: | Amino Acids |
| ISSN: | 1438-2199 0939-4451 |
| Popis: | 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 18O in the 3-hydroxyvaline sidechain when the acidic hydrolysis was performed in H2O/H218O (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 × L-2,3-diaminopropanoic acid. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink