NOVEL RETROVIRUS PROTEASE INHIBITORS, RPI-856-A, RPI-856-B, RPI-856-CAND RPI-856-D, PRODUCED BY STREPTOMYCES SP AL-322

Four kinds of retrovirus protease inhibitors (RPI-856 A, B, C and D) w ere isolated as white powder from the culture filtrate of a soil isola te, Streptomyces sp. AL-322 by column chromatography using Diaion HP-2 0, Sephadex LH-20, ODS reversed phase HPLC and SP-2SW ion exchange HPL C. The structures of these inhibitors were elucidated by physico-chemi cal properties, chemical reactions and spectral analyses, as valyl-ADP AA-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 a cid]. RPI-856 A and B, and RPI-856 C and D were both determined to be diastereomers each other on the asymmetric carbon in AOPBA. These four inhibitors strongly inhibited in vitro HIV-1 protease and HTLV-I prot ease both derived from recombinant Escherichia coli with IC50 of 10(-7 ) similar to 10(-8) M.