Isolation and structure of Sch 351633: A novel hepatitis C virus (HCV) NS3 protease inhibitor from the fungus Penicillium griseofulvum

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 14, 1999, Pages 1949-1952

  Chu, Min ^a   Mierzwa, Ronald ^a   He, Ling ^a   King, Arthur ^a   Patel, Mahesh ^a   Pichardo, John ^a   Hart, Andrea ^a   Butkiewicz, Nancy ^a   Puar, Mohindar S ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETAL DERIVATIVE; LACTONE DERIVATIVE; PROTEINASE INHIBITOR; SCH 351633; UNCLASSIFIED DRUG;

ARTICLE; DRUG ISOLATION; DRUG STRUCTURE; HEPATITIS C; PENICILLIUM; STRUCTURE ACTIVITY RELATION;

ANTIVIRAL AGENTS; INHIBITORY CONCENTRATION 50; LACTONES; MAGNETIC RESONANCE SPECTROSCOPY; MOLECULAR STRUCTURE; MOLECULAR WEIGHT; PENICILLIUM; SERINE PROTEINASE INHIBITORS; VIRAL NONSTRUCTURAL PROTEINS;

EID: 0033584192     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00321-2     Document Type: Article

References (8)

1. Choo, Q.-L.; Kuo, G.; Weiner, A. J.; Overby, L. R.; Bradley, D. W.; Houghton, M. Science 1989, 244, 359.
2. Kuo, G.; Choo, Q.-L.; Alter, H. J.; Gitnick, G. L.; Redeker, A. G.; Purcell, R. H.; Miyamuza, T.; Dienstag, J. L.; Alter, M. J.; Stevens, C. E.; Tegtmeier, G. E.; Bonino, F.; Colombo, M.; Lee, W.-S; Kuo, C.; Berger, K.; Shuster, J. R.; Overby, L. R.; Bradley, D. W.; Houghton, M. Science 1989, 244, 362.
3. Alter, M. J.; Hadler, S. C.; Judson, F. N.; Mares, A.; Alexander, W. J.; Hu, P. J.; Miller, J. K.; Moyer, L. A.; Fields, H. A.; Bradley, D. W.; Margolis, H. S. J. Am. Med. Assoc. 1990, 264, 2231.
4. Bresters, D. In Hepatitis C. Virus Reesink, H. W. Ed.; Karger: Basel, 1994, pp 121-136.
5. Chu, M.; Mierzwa, R.; Truumees, I.; King, A,; Patel, M.; Berrie, R.; Hart, A.; Butkiewicz, N.; DasMahapatra, B.; Chan, T-M.; Puar, M. S. Tetrahedron Lett. 1996, 37, 7229.
6. The fungus was supplied by Mr. G. M. Luedemann.
7. 3) δ 168.1, 164.1, 146.3, 145.8, 132.1, 132.1, 131.5, 131.5, 129.4, 127.7 112.7, 106.7, 88.1, 60.9.
8. 3H-labeled at the C-terminus. After incubation at 22 °C for 2 h, the reaction was stopped, and cleavage of the Cys-Ser bond was detected by the addition of streptavidin-coated SPA beads (Amersham), which can bind to the biotin-labeled peptide. Signal is detected as cpm using a Packard Topcount Model NXT instrument. Cleavage is indicated by reduction in signal caused by separation of the radiolabeled fragment from the bound biotinylated fragment, which is proportional to proteolytic activity.