Racemic crystal structures of peptide toxins, GsMTx4 prepared by protein total synthesis

The Piezo channel is a versatile mechanosensitive cation channel that mediates tactile, vascular development, and proprioception. GsMTx4 is the only reported inhibitor specifically targeting Piezo channels. Although the sequence of GsMTx4 is reported, the crystal structure of GsMTx4 is still unknown. Here, we achieved the two-segment synthesis of GsMTx4 and its enantiomer, enGsMTx4, through hydrazide based Native Chemical Ligation, and analyzed the crystal structure of GsMTx4 through the racemic crystallization technology. By analyzing the structure, we found that there is a hydrophobic patch surrounded by aromatic residues and charged residues.