SYNTHESIS OF PHILANTHOTOXIN ANALOGS WITH A BRANCHED POLYAMINE MOIETY

Philanthotoxin (PhTX-433), a potent noncompetitive inhibitor of the L- glutamate receptors and the nicotinic acetylcholine receptors of verte brates and invertebrates, has a butyryl-tyrosyl-thermo-spermine struct ure. Several synthetic analogs of PhTX with hydrophobic alkyl branches in the polyamine chain exhibit 6- to 10-fold enhanced activities to v arious receptors. Because the branched analogs exhibit such unique act ivities and because of their importance in tertiary structural studies of ligand/receptor binding, methods for preparing branched PhTX analo gs, including photolabile analogs, are presented.