Sch 65676: A novel fungal metabolite with the inhibitory activity against the cytomegalovirus protease

Tetrahedron Letters

Volumn 37, Issue 23, 1996, Pages 3943-3946

  Chu, Min ^a   Mierzwa, Ronald ^a   Truumees, Imbi ^a   King, Arthur ^a   Patel, Mahesh ^a   Pichardo, John ^a   Hart, Andrea ^a   Dasmahapatra, Bimal ^a   Das, Pradip R ^a   Puar, Mohindar S ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEINASE INHIBITOR; SCH 65676; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CYTOMEGALOVIRUS; DRUG ANALYSIS; DRUG DEVELOPMENT; DRUG ISOLATION; DRUG STRUCTURE; ENZYME INHIBITION; FERMENTATION; FUNGUS; NUCLEAR MAGNETIC RESONANCE;

CYTOMEGALOVIRUS; FUNGI;

EID: 15844364385     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00748-4     Document Type: Article

References (10)

1. Welch, A.R.; McNally, L.M.; Gibson, W. J. Virol., 1991, 65, 4091-4100.
2. Welch, A.R.; Woods, A.S.; McNally, L.M.; Cotter, R.J.; Gibson, W. Proc. Natl. Acad. Sci. 1991, 88, 10792-10796.
3. Jones, T.R.; Sun, L.; Bebernitz, G.A.; Muzithras, V.P.; Kim, H-J.; Johnston, S.H.; Baum, E.Z. J. Virol. 1994, 68, 2742-3752.
4. Sardana, V.V.; Wolfgang, J.A.; Veloski, C.A.; Long, W.J.; LeGrow, K.; Wolanski, B.; Emini, E.A.; LaFemina, R.L. J. Biol. Chem. 1994, 269, 14337-14340.
5. Alford, C.A.; Britt, W.J.: Cytomegalovirus. In Virology 2nd Ed., Knipe, D.M.; Fields, B.N. Eds.; Raven Press: New York, 1990, Vol. 2, pp. 1981-2010.
6. CMV protease assay: Standard protease assays were initiated by the addition of 0.06 μM purified CMV protease to 50 μM substrate peptide (Ala-Gly -Val-Val-Asp-Ala-Ser-Cys-Arg-Leu-Ala) in a 120 μ1 volume containing 50 mM of HEPES pH 7.5, 1 mM DTT, 0.1 mM EDTA, 20% glycerol, 2% DMSO, followed by incubation for 90 min at 30°C. Compounds to be tested were added prior to the addition of the protease. Reactions were terminated by the addition of 10% TFA (final concentration 0.1%). Cleavage products were analyzed in a reversed phase HPLC C-18 column and were estimated by area under the curve.
7. The fungus was supplied by Dr. B. Katz from MYCOsearch Lab.
8. 2O (5:3:3:5) solvent system, up layer used as mobile phase, 10 mL/min. HPLC Conditions: YMC PVA-SIL 20 × 250 mm semi-preparative column, S-5, 50-90% EtOAc in hexane with a linear gradient in 20 min, 12 mL/min, UV = 260 nm.
9. (a) Kaise, H.; Shinokara, M.; Miyazaki, W.; Izawa, T.; Nakano, Y.; Sugawaza, M.; Sugiura, K. J. Chem. Soc. Chem. Comm. 1979, 726-727.
10. (b) Ayer, W.A.; Miao, S. Can. J. Chem. 1993, 71, 487-493.