Provided is an oligonucleotide comprising the sequence R, YZR2 wherein R, and R2 are selected from the group consisting of a lipophilic substituted nucleotide analogue (L), a nucleotide, and a linkage, where in at least one of R, and R2 is a lipophilic substituted nucleotide analogue (L), where in Y is a pyrimidine nucleotide and wherein Z is a purine, a pyrimidine, or an abasic residue, wherein L is selected from a 5-chloro-uracil, 5-bromo-uracil, 5-iodo-uracil, 5-ethyl-uracil, or (E)-5-(2-bromovinyl)-uracil, with the proviso that the oligonucleotide is not 10 d[GCGAA(BrU)(BrU)CGC] where BrU is 5-bromo-uracil.