Naturally occurring protease inhibitors potent against the human immunodeficiency virus.
Inhibition of protease enzymes can render the human immunodeficiency virus (HIV) non-infectious in vitro. To enhance bioavailability and pharmacokinetic activity, 86 new blocking agents against HIV-I protease are derived by screening genome sequences from naturally occurring enzymes. The new agents are rank-ordered according to their chemical distance from a known set of HIV-protease inhibitors; the scoring methods have previously demonstrated 92% success in classifying a given amino acid sequence prior to testing for antiviral potency. The work has: 1) generalized the empirical work on HIV-PR to more than double the number of published peptides for blocking PR activity; 2) rank-ordered the inhibitors according to their chemical distance from the consensus sequence; 3) identified at least 28 gut enzymes with known bioavailability (> 10%) in vivo; 4) classified the family groupings of protease inhibitors in a hierarchical tree. Compared to the library of best known peptides, 19 of the natural sequences are closer to the consensus library than existing inhibitors.
Noever
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Faculty of Pharmaceutical Sciences, Protease Inhibitor Laboratories, Inc., Belle Mina, Alabama 35615, USA.
D000595:Amino Acid Sequence; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D010802:Phylogeny; D014779:Virus Replication / Q000187:drug effects*
D017320:HIV Protease Inhibitors; D009842:Oligopeptides