The disulfide framework V (CC---CC) is widely distributed as a component of Conus venoms and shows vast sequence diversity with little conservation of pharmacology.1 In this work we investigate its use as a turn scaffold by grafting residues (GYKL) that are present in the pharmacophore turn structure of conotoxin MrIA2 into the sequence, VCCGYKLCC. Surprisingly, under oxidative folding conditions an unexpected fourth disulfide bond isomer was obtained. Further investigation by regioselective disulfide bond formation demonstrated that altering the order of disulfide bond formation in the globular peptide led to topological isomers. We present here the synthesis, thermodynamic stability, 3D structure and function at the hNET transporter of these isomers. This work describes a rare example of the existence of stable topological isomers of cysteine rich peptides.3 This has implications for disulfide rich peptide discovery and synthesis, where the nature of the bioactive molecule may be determined not only by its disulfide connectivity but also by the existence of additional conformational isomers.