In mammals, about 40 isoforms of voltage-gated potassium channels (KVs) have been found. To study such a variety of KVs, substances are needed that are able to selectively bind to them and change their properties. We have previously reported on the isolation and pharmacological characterization of MeKTx13-3, a peptide toxin from the venom of the scorpion Mesobuthus eupeus. The toxin has shown high affinity to a number of KVs, with little selectivity for the KV1.1 isoform. In this paper, we describe the production of an artificial derivative of MeKTx13-3, named MeKTx13-3_RMRH, using rational design. The selectivity of MeKTx13-3_RMRH in relation to KV1.1 is increased by an order of magnitude making it one of the most specific ligands of this KV isoform. Finally, using computer simulations, we demonstrate that the preference of the new ligand to KV1.1 can be realized through a specific positioning of the toxin in complex with the channel.