Rational drug design of DNA oligonucleotides as HIV inhibitors.
DNA oligonucleotides as anti-HIV therapeutic agents have been developed for more than a decade. Numbers of oligonucleotides have been designed as potential anti-HIV inhibitors. Here we summarized the designed anti-viral oligonucleotides in last decade and divided the designed DNA HIV inhibitors into three categories: (i) antisense inhibitors, (ii) triplex inhibitors and (iii) G-quartet inhibitors, based upon their inhibitory mechanism and structures. Also we proposed a strategy of rational drug design of anti-HIV oligonucleotides, which includes several critical steps, such as (1) structure-based rational drug design, (2) chemical synthesis/combinational chemistry, (3) the determination of structural properties, (4) assays of the inhibition of HIV-1 IN and virus replication, and (5) 3D QSAR operation. This methodology has been used by the design of G-quartet inhibitors.
Jing
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Division of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. njing@bcm.tmc.edu
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D019380:Anti-HIV Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D009841:Oligonucleotides / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense