Chemical synthesis of analogs of the glycopeptide contulakin-G, an analgetically active conopeptide from Conus geographus

Abstract

Cone snails are marine predators that use immobilizing venoms for catching prey. Chemical analysis of the venoms has revealed a variety of biologically active small and intermediate size peptides rich in post-translational modifications (modified amino acids, glycosylation). The glycopeptide contulakin-G(pGlu-Ser-Glu-Glu-Gly-Gly-Ser-Asn-Ala-[beta-D-Galp-(1 -> 3)-alpha-D-GalpNAc(I ->]Thr-Lys-Lys-Pro-Tyr-Ile-Leu-OH) is a potent analgesic from Conus geographus venom. The in vivo activity of synthetic contulakin-G was previously found to be significantly higher compared to that of a peptide lacking the glycan. In order to further investigate the importance of the glycan, we have now synthesized analogs of contulakin-G where the glycan chain O-linked to threonine has been altered either to beta-D-Galp-(1 -> 3)-P-D-GalpNAc-, alpha-D-Galp-(1 -> 3)-alpha-D-GalpNAc-, or beta-D-Galp-(1 -> 6)-alpha-D-GalP-NAc-. The glycopeptides were assembled on a Wang resin using commercially available Fmoc amino acids and synthetically prepared Fmoc-protected threonine derivatives carrying O-acetyl protected sugar chains. The final products were thoroughly characterized by NMR and mass spectroscopy. (c) 2005 Elsevier Ltd. All rights reserved

Published in

Carbohydrate Research
2006, volume: 341, number: 1, pages: 9-18
Publisher: ELSEVIER SCI LTD

SLU Authors

• Norberg, Thomas

  • Department of Molecular Sciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Agricultural Science

Publication identifier

• DOI: https://doi.org/10.1016/j.carres.2005.11.010

Permanent link to this page (URI)

https://res.slu.se/id/publ/8975