Oligonucleotides can be designed to bind to oligopurine oligopyrimidine sequences of double-helical DNA. Binding occurs in the major groove and a triple helix is formed. Bifunctional oligonucleotide-intercalator conjugates have an increased affinity due to intercalation either at the triplex-duplex junction or within the triple-helical structure. Some intercalating agents can be chemically or photochemidally activated to induce irreversible reactions at the target sequence. Oligonucleotide directed triple-helix formation can be used to control gene transcription. Chimeric oligonucleotides can also be designed to form a triple helix on a single-stranded target. These ''oligonucleotide clamps'' can block nucleic acid processing enzymes.