Rational drug design: the proteinase inhibitors
Wlodawer, A.
PharmacoTherapy 14(6 Pt 2): 9S
1994
ISSN/ISBN: 0277-0008 PMID: 7885983 Document Number: 425005
Human immunodeficiency virus (HIV) proteinase is a promising target for the rational development of drugs against the acquired immunodeficiency syndrome (AIDS), since this enzyme is necessary for viral maturation, and its inhibition could lead to cessation of viral replication. Rational drug design combines chemical synthesis of compounds with structure determination methods, including protein crystallography. When the crystal structure of the HIV proteinase was determined, many research laboratories began designing drugs that would be effective inhibitors of the enzyme, and many such inhibitors were produced. Once that work was initiated, refined, and completed in the laboratory, other issues, such as specificity and bioavailability, became important. The clinical utility of such compounds is the final and most important consideration. Analysis of many agents for which structural formulas have been determined, and comparison of such formulas, provide valuable lessons for the continuing work on this enzyme and for future programs of rational drug design.