I am a
Home I AM A Search Login

Papers of the Week

Papers: 13 Jun 2020 - 19 Jun 2020

Animal Studies, Pharmacology/Drug Development

2020 Jun 07

Biochem Pharmacol

Pharmacological activity and NMR solution structure of the leech peptide HSTX-I.


McMahon KL, Tay B, Deuis JR, Tanaka BS, Peigneur S, Jin A-H, Tytgat J, Waxman SG, Dib-Hajj SD, Vetter I, Schroeder CI
Biochem Pharmacol. 2020 Jun 07:114082.
PMID: 32524995.


The role of voltage-gated sodium (Na) channels in pain perception is indisputable. Of particular interest as targets for the development of pain therapeutics are the tetrodotoxin-resistant isoforms Na1.8 and Na1.9, based on animal as well as human genetic studies linking these ion channel subtypes to the pathogenesis of pain. However, only a limited number of inhibitors selectively targeting these channels have been reported. HSTX-I is a peptide toxin identified from saliva of the leech Haemadipsa sylvestris. The native 23-residue peptide, stabilised by two disulfide bonds, has been reported to inhibit rat Na1.8 and mouse Na1.9 with low micromolar activity, and may therefore represent a scaffold for development of novel modulators with activity at human tetrodotoxin-resistant Na isoforms. We synthetically produced this hydrophobic peptide in high yield using a one-pot oxidation and single step purification and determined the three-dimensional solution structure of HSTX-I using NMR solution spectroscopy. However, in our hands, the synthetic HSTX-I displayed only very modest activity at human Na1.8 and Na1.9, and lacked analgesic efficacy in a murine model of inflammatory pain.