Cone snails (Conidae) are marine predators with some extraordinary features. 
Their venom contains a hundred or more peptides that target numerous ion 
channels and receptors in mammals, including several that are involved in 
disease. omega-Conotoxins from fish hunting snails are 24-27 residue peptides 
with a rigid 4-loop cysteine framework that target the N-type voltage-gated 
calcium channel (VGCC). Two omega-conotoxins, MVIIA and CVID are currently in 
clinical development for chronic pain management (Ziconotide or Prialt, and 
AM336, respectively). In an attempt to develop small molecule equivalents of 
CVID, we defined the Calpha-Cbeta vectors of the residues believed to be 
important for binding to the N-type VGCC. Using these vectors, we undertook a 
virtual screening of virtual libraries approach to identify compounds that 
matched the pharmacophore. Cyclic pentapeptides containing residues of loop 2 of 
CVID, with one or more being a D-amino acid were designed and synthesised and 
were found to be active at the N-type VGCC (IC50 approximately 20 microM). 
Agreeing with the specificity profile of CVID, molecules were inactive at the 
P/Q-type VGCC.