Diversity-oriented solid-phase synthesis and biological evaluation of oligonucleotide hairpins as HIV-1 RT RNase H inhibitors.

ABSTRACT: The inhibitory potencies of several hairpins comprising DNA, RNA and 2',5'-linked RNA segments were assessed against the RNase H activity of the human immunodeficiency virus reverse transcriptase (HIV-1 RT), an indispensable enzyme for HIV genomic replication. The hairpin library was constructed via diversity-oriented nucleic-acid synthesis (DONAS), an approach inspired from traditional split-pool synthesis. DONAS provided access to an array of oligonucleotide hairpins possessing distinct conformational, structural and biological properties. The inhibitory potency of these compounds was highly specific towards HIV-1 RT RNase H and strongly depended on the structure of both the stem and tetraloop. Hairpins that have an overall A-type geometry are better inhibitors of RNase H activity than h

SUBMITTER: Hannoush RN 

PROVIDER: S-EPMC535663 | biostudies-literature | 2004

REPOSITORIES: biostudies-literature