Investigation of substrate properties of DNA duplexes with covalently connected strands has been performed. The kinetic measurements of the hydrolysis processes of these compounds by snake venom phosphodiesterase has been carried out. It has been shown that the exonuclease stability of cross-linked DNA duplexes is greatly increased as compared with analogs without linkages between strands. The interaction of cross-linked DNA duplexes with the p50 subunit of human nucleic transcription factor of the kappa light-chain enhancer (NF-kappaB) has been studied. The presence of linkages between strands did not prevent the binding of protein with DNA duplexes and, in specific cases, even promoted this process. The speculation of using cross-linked DNA duplexes as efficient decoys for DNA-binding proteins such as NF-kappaB from the point of view of sense technology are discussed.