Carnivorous marine molluscs of the Conus genus possess potent paralytic venoms which comprise an enormous array of disulfide-rich peptides known as conotoxins. These peptides exhibit high affinity and specificity for important neurophysiological receptors and ion channels and have thus been adopted as biomedical research tools and therapeutic drug leads. The α-conotoxin subfamily are characterised by their antagonism of nicotinic acetylcholine receptor (nAChR) subtypes and two-disulfide bond framework and display analgesic properties in various rodent models of chronic pain.  Several members of this family also inhibit high voltage-activated calcium channels (HVACCs) via a novel GABA_B receptor-mediated mechanism. We have recently shown that highly conserved 8-residue, single-disulfide motif, known as [Ser3]Vc1.1(1-8) (sequence: GCSSDPRC), acts as an antagonist of both α7 nAChRs and HVACCs and is analgesic in a model of chronic visceral hypersensitivity. However, the key molecular mechanisms governing the in vitro and in vivo pharmacology of [Ser3]Vc1.1(1-8) are still poorly understood. In order to elucidate important determinants of peptide structure and function, we have chemically synthesised a library of analogues including positional mutants, disulfide-bond mimetics, truncations, cyclisation and lipidation. Characterisation of [Ser3]Vc1.1(1-8) analogues was performed using a combination NMR spectroscopy and electrophysiology to establish structure-activity relationships and determine candidates for further development as analgesic therapeutics.