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Synthesis, biological activity and isomerism of guanylate cyclase C-activating peptides guanylin and uroguanylin

Title data

Klodt, Joachim ; Kuhn, Michaela ; Marx, Ute C. ; Martin, Silke ; Rösch, Paul ; Forssmann, Wolf-Georg ; Adermann, Knut:
Synthesis, biological activity and isomerism of guanylate cyclase C-activating peptides guanylin and uroguanylin.
In: The Journal of Peptide Research. Vol. 50 (September 1997) Issue 3 . - pp. 222-230.
ISSN 1747-0285
DOI: https://doi.org/10.1111/j.1399-3011.1997.tb01188.x

Abstract in another language

Recently, the peptides guanylin and uroguanylin were identified as endogenous ligands of the membrane-bound guanylate cyclase C (GC-C) that is mainly expressed in the intestinal epithelium. In the present study, bioactive guanylin and uroguanylin have been prepared by solid-phase methodology using Fmoc/HBTU chemistry. The two disulfide bonds with relative 1/3 and 2/4 connectivity have been introduced selectively by air oxidation of thiol groups and iodine treatment of Cys(Acm) residues. Using this strategy, several sequential derivatives were prepared. Temperature-dependent HPLC characterization of the bioactive products revealed that guanylin-related peptides exist as a mixture of two compounds. The isoforms are interconverted within approximately 90 min, which prevents their separate characterization. This effect was not detected for uroguanylin-like peptides. Synthetic peptides were tested for their potential to activate GC-C in cultured human colon carcinoma cells (T84), known to express high levels of GC-C. The results obtained show that both disulfide bonds are necessary for GC-C activation. The presence of the amino-terminally neighboring residues of Cys104 for guanylin and Cys100 for uroguanylin has been found to be essential for GC-C stimulation. Unexpectedly, a hybrid peptide obtained from substitution of the central tripeptide AYA of guanylin by the tripeptide VNV of uroguanylin was not bioactive.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Biopolymers - Univ.-Prof. Dr. Paul Rösch
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biopolymers
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 15 Jan 2019 13:47
Last Modified: 16 May 2019 05:37
URI: https://eref.uni-bayreuth.de/id/eprint/46908