Protein cross-linking properties of the antitumor agent inosine dialdehyde (NSC-118994)

Inosine dialdehyde (IdA), a new antitumor agent presently undergoing clinical evaluation in man, possesses two aldehyde groups that form stable complexes with a variety of biologic molecules containing amino groups. Complex formation of IdA with lysine, glycine, histidine, or bovine serum albumin (BSA) greatly reduces the cytotoxicity of IdA against L1210 leukemia in vitro. Complexes of IdA and BSA exhibit molecular weights ranging from 69,000 to greater than 800,000 as determined by Sephadex G-200 gel filtration, indicating that both aldehyde groups of IdA are functional and can cross-link protein molecules. The cross-linking of plasma proteins and the cross-linking of glycine to BSA were also observed. No interaction of IdA with nucleic acids, nucleic acid bases, or nucleosides was detected. The dialdehyde derivatives of other nucleosides also possessed cross-linking properties.