Deziel R, Malenfant E; International Conference on Antiviral Research.
Antiviral Res. 1998 Mar; 37: A68 (abstract no. 102).
Bio-Mega Research Division, Boehringer Ingelheim Ltd., Quebec, Canada.
Human cytomegalovirus, like all the herpesviruses, encodes a unique serine protease which is necessary for viral replication. The recent determination of the X-ray structure of the HCMV N-terminal protease domain (NO) of gene UL80 revealed that this enzyme belongs to a novel class of serine proteases. The active site is composed of a triad consisting of His63, His157 and Ser132. Since their discovery, herpesvirus proteases have become attractive molecular targets for the design of novel antiviral drugs. We recently reported a series of substrate-based activated carbonyl inhibitors of the title protease in which we described a peptide beta-lactam derivative (Ogilvie et al, J. Med. Chem 1997). We now report a new series of non-peptidic monocyclic beta-lactam inhibitors. The structure-activity relationship work that led to the discovery of these small, potent and selective molecules will be disclosed. The mechanisms of inhibition of the HCMV protease by these new beta-lactams will also be discussed.
Publication Types:
Keywords:
- Antiviral Agents
- Binding Sites
- Cytomegalovirus
- Endopeptidases
- Herpesviridae
- Humans
- Monobactams
- Peptide Hydrolases
- Research
- Serine Endopeptidases
- Simplexvirus
- Structure-Activity Relationship
- assemblin
- beta-Lactams
Other ID:
UI: 102236617
From Meeting Abstracts