Synthesis of the Most Potent Isomer of μ-Conotoxin KIIIA Using Different Strategies.

ABSTRACT: In the chemical synthesis of conotoxins with multiple disulfide bonds, the oxidative folding process can result in diverse disulfide bond connectivities, which presents a challenge for determining the natural disulfide bond connectivities and leads to significant structural differences in the synthesized toxins. Here, we focus on KIIIA, a μ-conotoxin that has high potency in inhibiting Nav1.2 and Nav1.4. The non-natural connectivity pattern (C1-C9, C2-C15, C4-C16) of KIIIA exhibits the highest activity. In this study, we report an optimized Fmoc solid-phase synthesis of KIIIA using various strategies. Our results indicate that free random oxidation is the simplest method for peptides containing triple disulfide bonds, resulting in high yields and a simplified process. Alternatively, the se

SUBMITTER: Jian X 

PROVIDER: S-EPMC10143212 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature