Abstract:
:A survey of isosteric replacements of the phosphonoalanine side chain coupled with a process of conformational constraint of a bisbenzimidazole-based, Zn(2+)-dependent inhibitor of hepatitis C virus (HCV) NS3 serine protease resulted in the identification of novel series of active compounds with extended side chains. However, Zn(2+)-dependent HCV NS3 inhibition was relatively insensitive to the structural variations examined but dependent on the presence of negatively charged functionality. This result was interpreted in the context of an initial electrostatic interaction between protease and inhibitor that is subsequently consolidated by Zn(2+), with binding facilitated by the featureless active site and proximal regions of the HCV NS3 protein.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Yeung KS,Meanwell NA,Qiu Z,Hernandez D,Zhang S,McPhee F,Weinheimer S,Clark JM,Janc JWdoi
10.1016/s0960-894x(01)00457-7subject
Has Abstractpub_date
2001-09-03 00:00:00pages
2355-9issue
17eissn
0960-894Xissn
1464-3405pii
S0960894X01004577journal_volume
11pub_type
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