Publication Date:
1990-01-26
Description:
A synthetic peptidemimetic substrate of the human immunodeficiency virus 1 (HIV-1) protease with a nonhydrolyzable pseudodipeptidyl insert at the protease cleavage site was prepared. The peptide U-81749 inhibited recombinant HIV-1 protease in vitro (inhibition constant Ki of 70 nanomolar) and HIV-1 replication in human peripheral blood lymphocytes (inhibitory concentration IC50 of 0.1 to 1 micromolar). Moreover, 10 micromolar concentrations of U-81749 significantly inhibited proteolysis of the HIV-1 gag polyprotein (p55) to the mature viral structural proteins p24 and p17 in cells infected with a recombinant vaccinia virus expressing the HIV-1 gag-pol genes. The HIV-1 like particles released from inhibitor-treated cells contained almost exclusively p55 and other gag precursors, but not p24. Incubation of HIV-like particles recovered from drug-treated cultures in drug-free medium indicated that inhibition of p55 proteolysis was at least partially reversible, suggesting that U-81749 was present within the particles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McQuade, T J -- Tomasselli, A G -- Liu, L -- Karacostas, V -- Moss, B -- Sawyer, T K -- Heinrikson, R L -- Tarpley, W G -- New York, N.Y. -- Science. 1990 Jan 26;247(4941):454-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Infectious Disease Research Unit, Upjohn Company, Kalamazoo, MI 49001.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2405486" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Antiviral Agents/*pharmacology
;
DNA, Viral/genetics
;
Endopeptidases/*metabolism
;
Fusion Proteins, gag-pol/genetics/metabolism
;
Gene Products, gag/metabolism
;
HIV Protease
;
HIV-1/*drug effects/genetics/physiology
;
Humans
;
Lymphocytes/microbiology
;
Molecular Sequence Data
;
Molecular Structure
;
Oligopeptides/*pharmacology
;
Protease Inhibitors/*pharmacology
;
Protein Precursors/metabolism
;
RNA, Viral/metabolism
;
Transfection
;
Virus Replication/drug effects
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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