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

Cross-strand homo purine-purine (G-G or A-A) stacks and sheared purine puri ne pairing have been found to be important motifs in nucleic acid duplex st ructures. We now report novel cross-strand purine-pyrimidine (A-C) and hete ro purine-purine (G-A) stacks that are established from a sheared purine.py rimidine (A . C) pair adjacent to a sheared G . A pair in the 5'-AA/GC-3' s equence This "internal loop" sequence is conserved in two families of singl e-stranded DNA inhibitors of the reverse transcriptase of type 1 human immu nodeficiency virus. The distorted backbone of these inhibitors, resulting f rom 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 inhi bitors as compared with other regular B-form duplex substrates. Two simple rules have been generalized to account for all reported cross-strand stacks . (C) 1999 Academic Press.