Books > Medicine > Other branches of medicine > Pharmacology
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Progress in Drug Research (Paperback, Softcover reprint of the original 1st ed. 1998)
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Discovery Miles 15 230
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Progress in Drug Research (Paperback, Softcover reprint of the original 1st ed. 1998)
Series: Progress in Drug Research, 51
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Due tothedevelopmentofdrugresistanceandotherlimitationsinthe treat-
ment of AIDS patients with reverse transcriptase (RT) inhibitors
like zidovu- dineandothers,
itbecamenecessarytoexploreantiviralagentsactingontar- getsotherthan
RT. Inthepastfewyears, hundredsofHIVproteaseinhibitoLs have been
synthesized and tested. Among these protease inhibitors,
saquinavir, ritonavir, indinavir and nelfinavir have been marketed
during 1995-1997. In this review, emphasis is placed on the
development of HIV protease inhibitors as antiviral agents against
HIV, structure-activity rela- tionship (SAR) analysis
ofsaquinavirand relatedcompounds, comparisonof four marketed HIV
protease inhibitors, and future prospect in developing new anti-HIV
drugs. 2 Introduction HIV protease inhibitors 3 HIV protease as a
target for chemotherapy HIV protease was first suggested as a
potential target for AIDS therapy by Kramer et a1. in 1986 [5]. HIV
protease is a proteolytic enzyme responsible for cleaving large
numbers of amino acid sequences. This enzyme regulates
conversionoftheselargeaminoacid sequencesintobiologicallyactive
struc- tural and functional protein products. Specifically, HIV
protease is responsi- the enzymatic processing of the gagand
gag-pol genes of HIV, which ble for encode for functional core
proteins and viral enzymes (reverse transcriptase, ribonuclease H,
integrase, and HIV protease). The polyproteins encoded by the
gagand gag-pol genes undergo post-translational processing by HIV
pro- tease to form functional protein products as the viral
particles budding out from infected cells. Therefore, inhibition of
HIV protease by a protease inhibitor results in the release
ofimmature, noninfectious viral particles [4].
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