Chemical synthesis of analogs of the glycopeptide contulakin-G, an analgetically active conopeptide from Conus geographus.
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-(1-->]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)-beta-D-GalpNAc-, alpha-D-Galp-(1-->3)-alpha-D-GalpNAc-, or beta-D-Galp-(1-->6)-alpha-D-GalpNAc-. 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.
Westerlind
Ulrika
U
Department of Chemistry, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden.
Norberg
Thomas
T
D000595:Amino Acid Sequence; D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D002240:Carbohydrate Sequence; D052078:Conus Snail; D006020:Glycopeptides / Q000138:chemical synthesis; D006023:Glycoproteins / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000138:chemical synthesis*
D000700:Analgesics; D006020:Glycopeptides; D006023:Glycoproteins; D009479:Neuropeptides; C119349:contulakin-G protein, Conus geographus