Synthesis and paralytic activities of squaryl amino acid-containing polyamine toxins

Summary.  Eight analogs 4a-7a and 4b-7b of philanthotoxin (PhTX) from wasp venom and nephilatoxin-8 (NPTX-8) from spider venom whose tyrosine or asparagine linker is replaced by squaryl (sq) amino acid or 4-amino squaryl (4-asq) amino acid have been synthesized in an efficient manner via coupling of N-acyl squaryl amino acid intermediate 19 or 26 with the corresponding polyamine part. Preliminary bioassay using crickets revealed that the analogs substituted by glutamate-type squaryl amino acid-containing NPTX 7a and 7b showed more potent paralytic activities than that of NPTX-8. Received April 25, 2002 Accepted June 21, 2002 Published online December 18, 2002 Acknowledgement This work was supported by a grant from Research for the Future Program from the Japan Society for the Promotion of Science (JSPS). Authors' address: Yasufumi Ohfune, Graduate School of Science, Osaka City University, Sugimoto, Osaka 558-8585, Japan, Fax: +81-6-6605-3153, E-mail: ohfune@sci.osaka-cu.ac.jp