Synthesis and biological evaluation of anthranilamide-based non-peptide mimetics of omega-conotoxin GVIA

Baell, Jonathan B., Duggan, Peter J., Forsyth, Stewart A., Lewis, Richard J., Lok, Y. Phei, Schroeder, Christina I. and Shepherd, Nicholas E. (2006) Synthesis and biological evaluation of anthranilamide-based non-peptide mimetics of omega-conotoxin GVIA. Tetrahedron, 62 31: 7284-7292. doi:10.1016/j.tet.2006.05.041


Author Baell, Jonathan B.
Duggan, Peter J.
Forsyth, Stewart A.
Lewis, Richard J.
Lok, Y. Phei
Schroeder, Christina I.
Shepherd, Nicholas E.
Title Synthesis and biological evaluation of anthranilamide-based non-peptide mimetics of omega-conotoxin GVIA
Formatted title
Synthesis and biological evaluation of anthranilamide-based non-peptide mimetics of ω-conotoxin GVIA
Journal name Tetrahedron   Check publisher's open access policy
ISSN 0040-4020
Publication date 2006-07
Sub-type Article (original research)
DOI 10.1016/j.tet.2006.05.041
Volume 62
Issue 31
Start page 7284
End page 7292
Total pages 9
Place of publication Oxford, England
Publisher Pergamon
Collection year 2006
Language eng
Subject C1
320305 Medical Biochemistry - Proteins and Peptides
780103 Chemical sciences
Formatted abstract
Non-peptide mimetics based on an anthranilamide 'scaffold' possessing fragments that mimic Lys2, Tyr13 and Arg17 in omega-conotoxin GVIA have been prepared. Compounds were assayed for binding to the voltage-gated calcium channels Cav2.2 ('N-type') and Cav2.1 'P/Q-type') in rat brain. The primary synthetic target, 2-(6-amino-hexanoylamino)-5-(3-guanidino-propoxy)-N-[4-(4-hydroxyphenoxy)phenyll -benzamide (2a), exhibited low mu M binding to Cav2.2 and was more than 30-fold selective for Cav2.2 over Cav2. 1.
Keyword Omega-conotoxin
Mimetic
Ca(v)2.2 ('N-type') calcium channel blocker
Neuronal Calcium-channels
N-type
Iii Mimetics
Shk Toxin
Design
Deprotection
Binding
Blocker
Pain
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 09:17:39 EST