Inhibition of activity of the protease from bovine leukemia virus.
In view of the close similarity between bovine leukemia virus (BLV) and human T-cell leukemia virus type I (HTLV-I) we investigated the possibility of developing specific inhibitors of the proteases of these retroviruses using the purified enzyme from BLV. We tested the ability of this protease to specifically cleave various short oligopeptide substrates containing cleavage sites of BLV and HTLV-I proteases, as well as a recombinant BLV Gag precursor. The best substrate, a synthetic decapeptide bearing the natural cleavage site between the matrix and the capsid proteins of BLV Gag precursor polyprotein, was used to develop an inhibition assay. We determined the relative inhibitory effect of synthetic Gag precursor-like peptides in which the cleavable site was replaced by a non-hydrolyzable moiety. The encouraging inhibitory effect of these compounds indicates that potent non-peptidic inhibitors for retroviral proteases are not unattainable.
INSERM Unité 328, fondation Bergonié, Bordeaux, France.
A
A
Ménard
R
R
Leonard
S
S
Llido
S
S
Geoffre
P
P
Picard
F
F
Berteau
G
G
Precigoux
M
M
Hospital
B
B
Guillemain
D000595:Amino Acid Sequence; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015683:Gene Products, gag / Q000737:chemistry / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000201:enzymology; D001909:Leukemia Virus, Bovine / Q000201:enzymology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010436:Pepstatins / Q000494:pharmacology; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011498:Protein Precursors / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
D015683:Gene Products, gag; D009842:Oligopeptides; D010436:Pepstatins; D011480:Protease Inhibitors; D011498:Protein Precursors; D011994:Recombinant Proteins; C014195:Streptomyces pepsin inhibitor; D010450:Endopeptidases; C031375:pepstatin