A search for vertebrate peptides containing D-amino acids
- Biotechnologie
- Nanowissenschaften und -technologie
Abstract
In multicellular organisms many vital functions are mediated by peptides. Some of these peptides contain a D-amino acid in a well-defined position. To date, in all vertebrates and several invertebrates the D-amino acid is the second residue of the mature peptide whereas it has been found in other positions in invertebrates. Vertebrate peptides comprise dermorphins, deltorphins, and the peptide antibiotics bombinin H from frog skin, as well as a C-type natriuretic peptide (CNP) and beta-defensin-like peptide (DLP) from the venom of male Platypus, a primitive mammal. In case of the opioid peptides, the all L-forms are inactive, whereas subtle differences in activity and physicochemical properties between the two diastereomers of bombinin H have been observed. From skin secretions of Bombinae, an enzyme has been isolated which catalyses the posttranslational inversion of the stereochemistry of the respective L-amino acids present in the precursor of bombinin H. This L/D-isomerase acts exclusively on the second residue. Genes encoding polypeptides related to the frog skin enzyme are present in many vertebrates including man supporting the idea of the existence of diastereomeric peptides in higher mammals. A detailed study of the substrate specificity of the frog isomerase and subsequent data base search has led to the identification of potential substrates, which include hormones, antibacterial peptides etc., for which a D-form could exist as well. Based on this knowledge, the proposed project mainly will focus on the questions, whether i) the diastereomeric form of a few selected peptides can be detected in animal tissues and thus the presence of the D-residue be directly confirmed, and ii) the biological activity and/or physicochemical properties of the peptides are modulated by the stereoinversion. In particular, the D-amino acid could crucially affect receptor interactions, folding propensities or polypeptide turnover in these peptides and thus have far-ranging consequences on their biological function.
Publications
Tight Binding of Transition-State Analogues to a Peptidyl-Aminoacyl-L/D-Isomerase from Frog Skin
Autoren: Gehmayr, V; Mollay, C; Reith, L; Muller, N; Jilek, A Jahr: 2011
Journal articles
Project staff
Alexander Jilek
Mag.Dr.rer.nat. Alexander Jilek
alex.jilek@gmx.at
Project Leader
01.01.2011 - 30.06.2013