Novel retrovirus protease inhibitors, RPI-856 A, B, C and D, produced by Streptomyces sp. AL-322.
Four kinds of retrovirus protease inhibitors (RPI-856 A, B, C and D) were isolated as white powder from the culture filtrate of a soil isolate, Streptomyces sp. AL-322 by column chromatography using Diaion HP-20, Sephadex LH-20, ODS reversed phase HPLC and SP-2SW ion exchange HPLC. The structures of these inhibitors were elucidated by physico-chemical properties, chemical reactions and spectral analyses, as valyl-ADPAA-leucyl-AOPBA-valyl-valyl-aspartic acid (RPI-856 A and B) and valyl-ADPAA-leucyl-AOPBA-valyl-valine (RPI-856 C and D) [ADPAA = 2-amino-2-(3,5-dihydroxyphenyl)acetic acid, AOPBA = 3-amino-2-oxo-4-phenylbutyric acid]. RPI-856 A and B, and RPI-856 C and D were both determined to be diasteromers each other on the asymmetric carbon in AOPBA. These four inhibitors strongly inhibited in vitro HIV-1 protease and HTLV-I protease both derived from recombinant Escherichia coli with IC50 of 10(-7) approximately 10(-8) M.
Discovery Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
T
T
Asano
K
K
Matsuoka
T
T
Hida
M
M
Kobayashi
Y
Y
Kitamura
T
T
Hayakawa
S
S
Iinuma
A
A
Kakinuma
K
K
Kato
D000595:Amino Acid Sequence; D005285:Fermentation; D015497:HIV-1 / Q000201:enzymology; D015368:Human T-lymphotropic virus 1 / Q000201:enzymology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011480:Protease Inhibitors / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D013053:Spectrophotometry; D013302:Streptomyces / Q000737:chemistry* / Q000145:classification
D009842:Oligopeptides; D011480:Protease Inhibitors; C088529:RPI 856 A; C088530:RPI 856 C