HIV-1 protease inhibitory activity of L-694,746, a novel metabolite of L-689,502.
L-689,502 is a potent inhibitor of HIV-1 protease activity in vitro. Microbial biotransformations of L-689,502 by cultures belonging to the genus Streptomyces sp. were performed. Extracts of culture broths were examined for the production of metabolites of L-689,502 that could inhibit HIV-1 protease activity. One culture, MA 6804 (Streptomyces lavendulae, ATCC 55095), produced L-694,746 that, while being structurally related to L-689,502, is a novel metabolite and a potent inhibitor of HIV-1 protease.
Lingham
R B
RB
Merck, Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.
Arison
B H
BH
Colwell
L F
LF
Hsu
A
A
Dezeny
G
G
Thompson
W J
WJ
Garrity
G M
GM
Gagliardi
M M
MM
Hartner
F W
FW
Darke
P L
PL
D000595:Amino Acid Sequence; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D017320:HIV Protease Inhibitors; D015497:HIV-1 / Q000201:enzymology*; D007700:Kinetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009025:Morpholines / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism; D010436:Pepstatins / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D013302:Streptomyces / Q000378:metabolism
D017320:HIV Protease Inhibitors; D009025:Morpholines; D009842:Oligopeptides; D010436:Pepstatins; D010455:Peptides; D011480:Protease Inhibitors; C014195:Streptomyces pepsin inhibitor; C072111:L 689502; C072112:L 694746; C031375:pepstatin