The dimethyl adenosine derivative originally isolated from Puromycin® produced a nephrotic syndrome in rats, but not in guinea pigs or rabbits. The urinary excretion products in these species were examined after injection of this compound.
All species excreted the dimethyl- and the monomethyl adenosine derivatives. The rat and rabbit excreted the adenosine derivative and the rabbit also excreted the inosine derivative. All species excreted monomethyl adenosine and/or dimethyl adenosine derivatives substituted most likely on the sugar.
The nephrotic syndrome was produced by injection of the monomethyl-, the methyl propyl-, and the diethyl adenosine derivatives, but not by the adenosine, inosine or dipropyl adenosine derivatives.
The dimethyl-, monomethyl-, and adenosine derivatives inhibited to approximately the same extent a crude adenosine kinase enzyme obtained from yeast. These three compounds were also converted to nucleotides by this preparation. The dimethyl adenosine derivative was the least effective nucleotide precursor.
It seems probable that several derivatives are capable of producing the nephrotic syndrome. The enzymatic locus of action may be adenosine kinase, but action at the nucleotide level has not been ruled out.
Methods are indicated for the isolation and characterization of this series of nucleosides and nucleotides.