Solid-phase synthesis of neuroactive spider-wasp hybrid toxin analogues using a backbone amide linker

Polyamine toxins isolated from the venoms of spiders and wasps and their synthetic analogues are uncompetitive antagonists of ligand-gated ionotropic receptors in the central- and peripheral nervous systems, and have proved valuable as tools for the investigation of receptor structure and function. In the present letter we describe the efficient solid-phase synthesis (SPS) of novel hybrid toxins using a BAL resin. This strategy enables the bidirectional construction of toxin molecules and has a potential in SPS of chemically diverse libraries of toxin analogues for structure-activity relationship (SAR) studies.

Graphical abstractThe efficient solid-phase synthesis (SPS) of novel hybrid toxins using a BAL resin is described. This strategy enables bidirectional construction of toxin molecules and has a potential in SPS of chemically diverse libraries of toxin analogues for structure-activity relationship (SAR) studies.Download full-size image