Novel approach to design an isosteric charge-deficient analogue of spermine and its biochemically important derivatives

The design and synthesis of SpmTrien (1,12-diamino-3,6,9-triazadodecane), an isosteric and charge-deficient analogue of spermine with excellent chelating properties towards Cu²⁺ ions, as well as novel N¹- and N¹²-Ac-SpmTriens and bis-Et-SpmTrien (N¹,N¹²-diethyl-1,12-diamino-3,6,9-triazadodecane) are described. Possible applications of SpmTrien and its derivatives to the investigation of the enzymes of polyamine metabolism and spermine cellular functions, including interaction with DNA, are discussed.