Engineering of highly potent and selective HNTX-III mutant against hNa_v1.7 sodium channel for treatment of pain.

ABSTRACT: Human voltage-gated sodium channel Na_v1.7 (hNa_v1.7) is involved in the generation and conduction of neuropathic and nociceptive pain signals. Compelling genetic and preclinical studies have validated that hNa_v1.7 is a therapeutic target for the treatment of pain; however, there is a dearth of currently available compounds capable of targeting hNav1.7 with high potency and specificity. Hainantoxin-III (HNTX-III) is a 33-residue polypeptide from the venom of the spider Ornithoctonus hainana. It is a selective antagonist of neuronal tetrodotoxin-sensitive voltage-gated sodium channels. Here, we report the engineering of improved potency and Na_v selectivity of hNa_v1.7 inhibition peptides derived from the HNTX-III scaffold. Alanine scanning

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC7988488 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature