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Schulz, Axel ; Escher, Sylvia E. ; Marx, Ute C. ; Meyer, Markus ; Rösch, Paul ; Forssmann, Wolf-Georg ; Adermann, Knut:
Carboxy-terminal extension stabilizes the topological stereoisomers of guanylin.
In: The Journal of Peptide Research.
Bd. 52
(1998)
Heft 6
.
- S. 518-525.
ISSN 1747-0285
DOI: https://doi.org/10.1111/j.1399-3011.1998.tb01256.x
Abstract
The peptide hormone guanylin constitutes two topological stereoisomers, which are connected through an equilibrium of interconversion. To investigate the importance of amino acid residues in the central region between the inner cysteines and at the carboxy terminus for this isomerism, synthetic derivatives of guanylin were compared by HPLC, 2D1H NMR spectroscopy and by their guanylyl cyclase-C (GC-C)-activating potency. An increase in the central sterical bulk by introduction of diiodo-Tyr9 had virtually no effect on the isomerization kinetics. Compared to guanylin, carboxy-terminal amidation did not affect the equilibrium between the two isoforms either. In contrast, two significantly stabilized isomers were obtained by extending the carboxy terminus of guanylin with one additional leucine resembling the characteristic of human uroguanylin isomers. This effect was intensified by a further Lys-Lys extension, thus revealing that the conformational exchange between the guanylin isomers is dependent on the extent of the sterical hindrance in the carboxy-terminal region of this peptide. Demonstrated by 2D NMR spectroscopy, the separated isomers of the carboxy-terminally extended derivatives of guanylin exhibit unambiguously closely related structures as found originally for guanylin isomers, which are only detectable as a mixture. Because only one of the stabilized guanylin isomers activates guanylyl cyclase-C, the three-dimensional structure of the GC-C-activating guanylin isomer is now defined. The stabilized isoforms of guanylin described in this study represent suitable tools for the separate functional investigation of the GC-C-agonistic isomer of guanylin as well as of its isomeric counterpart.
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| Publikationsform: | Artikel in einer Zeitschrift |
|---|---|
| Begutachteter Beitrag: | Ja |
| Institutionen der Universität: | Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Ehemalige Professoren > Lehrstuhl Biopolymere - Univ.-Prof. Dr. Paul Rösch Fakultäten Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Ehemalige Professoren Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Lehrstuhl Biochemie mit Schwerpunkt Biophysikalische Chemie |
| Titel an der UBT entstanden: | Ja |
| Themengebiete aus DDC: | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie |
| Eingestellt am: | 23 Jan 2019 08:14 |
| Letzte Änderung: | 07 Apr 2022 09:00 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/46989 |