Monofunctional, bifunctional and trifunctional poly-2'-(2,4-dinitrophenyl)-
oligoribunucleotides have been designed and synthesized as inhibitors of re
troviruses. These compounds are membrane-permeable, ribonuclease-resistant,
and apparently mutation-insensitive inhibitors of reverse transcriptases.
These inhibitors have been tested for the treatment of murine leukemia as a
n animal model related to AIDS. Although the monofunctional inhibitor is al
ready 100% effective for the treatment of murine leukemia, its efficacy can
be increased by two orders of magnitude by introducing antisense sequences
in the nucleotide backbone so that the resulting multifunctional inhibitor
can also disrupt the synthesis of specific viral proteins. The entropy adv
antage of multifunctionality in the design of antiviral agents is discussed
.