Synthesis and Cav2.2 Binding Data for Non-Peptide Mimetics of ω-Conotoxin GVIA based on a 5-Amino-Anthranilamide Core

Peter J. Duggan; Jonathan M. Faber; Janease E. Graham; Richard J. Lewis; Natalie G. Lumsden; Kellie L. Tuck

doi:10.1071/CH07327

RESEARCH ARTICLE

Synthesis and Ca_v2.2 Binding Data for Non-Peptide Mimetics of ω-Conotoxin GVIA based on a 5-Amino-Anthranilamide Core

Peter J. Duggan ^A , Jonathan M. Faber ^B , Janease E. Graham ^A ^B , Richard J. Lewis ^C , Natalie G. Lumsden ^C and Kellie L. Tuck ^B ^D

+ Author Affiliations

- Author Affiliations

^A CSIRO, Molecular and Health Technologies, Bag 10, Clayton South VIC 3169, Australia.

^B School of Chemisty, Monash University, Clayton VIC 3800, Australia.

^C Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.

^D Corresponding author. Email: kellie.tuck@sci.monash.edu.au

Australian Journal of Chemistry 61(1) 11-15 https://doi.org/10.1071/CH07327
Submitted: 13 September 2007 Accepted: 29 November 2007 Published: 18 January 2008

Abstract

A simple and efficient method has been developed for the synthesis of two anthranilamide-based non-peptide mimetics of ω-conotoxin GVIA. These anthranilamide derivatives aim to mimic the K2, R17, and Y13 residues of the peptide. The synthetic route described enables the rapid synthesis of anthranilamide analogues with identical alkyl chain lengths. The target compounds show affinity to rat N-type voltage gated calcium channels (Ca_v2.2) with EC₅₀ values of 42 and 75 μM.

Acknowledgements

The authors wish to acknowledge the Monash–CSIRO Collaborative Research Support Scheme for the funding for the present project as well as the top-up scholarship received by J.E.G. Monash University is also to be acknowledged for the MGS received by J.E.G.

References

^A 95% confidence intervals for diamines 3a and 3b are 11–520 and 8–220 μM, respectively.

^B It has not yet been proved that the K2-Y13-R17 mimetics bind to the N-type voltage gated calcium channels in the same manner as ω-conotoxin GVIA.^[24,26]

Synthesis and Cav2.2 Binding Data for Non-Peptide Mimetics of ω-Conotoxin GVIA based on a 5-Amino-Anthranilamide Core

Abstract

Acknowledgements

Subscriber Login

Synthesis and Ca_v2.2 Binding Data for Non-Peptide Mimetics of ω-Conotoxin GVIA based on a 5-Amino-Anthranilamide Core