Herpesvirus protease: Mechanistic studies and discovery of inhibitors of the human cytomegalovirus protease

Drug Design and Discovery

Volumn 15, Issue 1, 1997, Pages 3-15

  Flynn, Daniel L ^a   Becker, Daniel P ^a   Dilworth, Vickie M ^a   Highkin, Maureen K ^a   Hippenmeyer, Paul J ^a   Houseman, Kathryn A ^a   Levine, Leanna M ^a   Li, Madeleine ^a   Moormann, Alan E ^a   Rankin, Anne ^a   Toth, Mihaly V ^a   Villamil, Clara I ^a   Wittwer, Arthur J ^a   Holwerda, Barry C ^a  

^a PFIZER INC   (United States)

Author keywords

Antiviral; Assemblin; Herpesvirus protease; Inhibition

Indexed keywords

HYBRID PROTEIN; PROTEINASE; PROTEINASE INHIBITOR; RECOMBINANT PROTEIN; SULFOXIDE; VIRUS ENZYME;

AMINO TERMINAL SEQUENCE; ANTIVIRAL ACTIVITY; CARBOXY TERMINAL SEQUENCE; CELL CULTURE; CONFERENCE PAPER; CONTROLLED STUDY; DRUG MECHANISM; DRUG SCREENING; ENZYME INHIBITION; GENE STRUCTURE; HERPES VIRUS; HUMAN CYTOMEGALOVIRUS; NONHUMAN; OPEN READING FRAME; PROTEIN DOMAIN; SITE DIRECTED MUTAGENESIS; VIRUS GENOME; VIRUS INFECTION; VIRUS REPLICATION;

ANTIVIRAL AGENTS; CYTOMEGALOVIRUS; ENDOPEPTIDASES; HERPESVIRIDAE; HUMANS; PROTEASE INHIBITORS; SERINE ENDOPEPTIDASES;

EID: 8544281667     PISSN: 10559612     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Conference Paper

References (29)

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13. Co-elution of the "dimer" 16-kDa and 14-kDa fragments from the Ni-affinity column occurs even under reducing conditions when DTT is present. Furthermore, the two-chain form of the enzyme exhibits enhanced specific catalytic activity when assayed under reducing (DTT) conditions.
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27. These results also indicate that the inhibition of HCMV protease by the sulfoxide class of inhibitors is reversible by sulfhydryl agents (DTT) that are capable of restoring the enzyme to its reduced state. Indeed, incubation of inhibited enzyme with DTT restores catalytic activity.
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29. 50 > 100 μM) also demonstrate antiviral activity in the HCMV RC256 cell assay.