Cross-strand purine-pyrimidine stack and sheared purine.pyrimidine pairing in the human HIV-1 reverse transcriptase inhibitors.

Cross-strand homo purine-purine (G-G or A-A) stacks and sheared purine.purine pairing have been found to be important motifs in nucleic acid duplex structures. We now report novel cross-strand purine-pyrimidine (A-C) and hetero purine-purine (G-A) stacks that are established from a sheared purine.pyrimidine (A.C) pair adjacent to a sheared G.A pair in the 5'-AA/GC-3' sequence. This "internal loop" sequence is conserved in two families of single-stranded DNA inhibitors of the reverse transcriptase of type 1 human immunodeficiency virus. The distorted backbone of these inhibitors, resulting from the unique helical twists and kinks in the 5'-AA/GC-3' sequence, may be responsible for the increased affinities of these single-stranded DNA inhibitors as compared with other regular B-form duplex substrates. Two simple rules have been generalized to account for all reported cross-strand stacks.