Circular dichroism and NMR studies of metabolically stablealpha-methylpolyamines: spectral comparison with naturally occurring polyamines.

ABSTRACT

Three synthetic polyamine analogs, alpha-methylspermine, and alpha,alpha'-dimethylspermine, were compared with their naturally occurring counterparts, spermidine and spermine, by two different spectral techniques. The interaction of polyamines with oligodeoxynucleotides was measured by circular dichroism in order to monitor the polyamine-induced conversion of right-handed B-DNA to the left-handed Z-form. The methylated analogs were shown to be equally effective as the natural polyamines in inducing the B --> Z transition. The pH dependence of the chemical shift of all carbon atoms in each of the five polyamines was measured by (13)C-NMR spectroscopy. With the exception of expected changes in chemical shift due to the presence of the alpha-methyl substituents, the chemical shifts and pH dependence of all carbon atoms in the three alpha-methyl polyamines were similar to the corresponding naturally occurring polyamines. The combined data indicate that alpha-methyl polyamines have physical properties that are very similar to their natural counterparts. The two metabolically stable polyamine analogs, alpha-methylspermidine and alpha,alpha'-dimethylspermine, are therefore useful surrogates for spermidine and spermine in the study of numerous polyamine-mediated effects in mammalian cell cultures and can be used in such studies without the requirement for coadministration of amine oxidase inhibitors.