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Title: A Defined α-Helix in the Bifunctional O-Glycosylated Natriuretic Peptide TcNPa from the Venom of 'Tropidechis carinatus'
Contributor(s): Reeks, Timothy (author); Jones, Alun (author); Alewood, Paul F (author); Brust, Andreas (author); Sridharan, Sindhuja (author); Corcilius, Leo (author); Wilkinson, Brendan  (author)orcid ; Thaysen-Andersen, Morten (author); Payne, Richard J (author); Kini, R Manjunatha (author); Daly, Norelle L (author)
Publication Date: 2015
DOI: 10.1002/anie.201411914
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Abstract: Natriuretic peptides (NP) play important roles in human cardiac physiology through their guanylyl cyclase receptors NPR-A and NPR-B. Described herein is a bifunctional O-glycosylated natriuretic peptide, TcNPa, from 'Tropidechis carinatus' venom and it unusually targets both NPR-A and NPR-B. Characterization using specific glycosidases and ETD-MS identified the glycan as galactosyl-β(1-3)-N-acetylgalactosamine (Gal-GalNAc) and was α-linked to the C-terminal threonine residue. TcNPa contains the characteristic NP 17-membered disulfide ring with conserved phenylalanine and arginine residues. Both glycosylated and nonglycosylated forms were synthesized by Fmoc solid-phase peptide synthesis and NMR analysis identified an α-helix within the disulfide ring containing the putative pharmacophore for NPR-A. Surprisingly, both forms activated NPR-A and NPR-B and were relatively resistant towards proteolytic degradation in plasma. This work will underpin the future development of bifunctional NP peptide mimetics.
Publication Type: Journal Article
Source of Publication: Angewandte Chemie (International Edition), 54(16), p. 4828-4831
Publisher: Wiley-VCH Verlag GmbH & Co KGaA
Place of Publication: Germany
ISSN: 1521-3773
Field of Research (FOR): 030401 Biologically Active Molecules
030403 Characterisation of Biological Macromolecules
030406 Proteins and Peptides
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
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