The ability of DNA oligonucleotides, neutral peptide nucleic acids (PNAs), and oligonucleotide conjugates to hybridize to inverted repeat sequences within supercoiled double-stranded DNA by Watson-Crick base-pairing is examined. PNAs and oligonucleotide conjugates initiate and maintain strand invasion under more stringent conditions than do unmodified DNA oligonucleotides. PNAs hybridize rapidly and, once bound, hold open a target site allowing oligonucleotides to base-pair to the displaced strand under conditions that would otherwise preclude hybridization. The ability to manipulate hybridization efficiency through different options for the alteration of oligomer charge should have important implications for optimizing sequence-specific recognition of DNA.