De novo design and synthesis of a μ-conotoxin KIIIA peptidomimetic.

μ-Conotoxin KIIIA blocks voltage-gated sodium channels and displays potent analgesic activity in mice models for pain. Structure–activity studies with KIIIA have shown that residues important for sodium channel activity are presented on an α-helix. Herein, we report the de novo design and synthesis of a three-residue (Lys7, Trp8, His12) peptidomimetic based on a novel diketopiperazine (DKP) carboxamide scaffold.