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PDBsum entry 3bc4
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References listed in PDB file
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Key reference
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Title
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Targeting the open-Flap conformation of HIV-1 protease with pyrrolidine-Based inhibitors.
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Authors
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J.Böttcher,
A.Blum,
S.Dörr,
A.Heine,
W.E.Diederich,
G.Klebe.
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Ref.
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Chemmedchem, 2008,
3,
1337-1344.
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PubMed id
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Abstract
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HIV protease is a well-established drug target in antiviral chemotherapy.
Immense research efforts have been made to discover effective inhibitors, thus
making the enzyme one of the most studied and best characterized proteins.
Although the protease exhibits high flexibility, all approved drugs target
virtually the same protein conformation. The development of viral
cross-resistance demands the generation of inhibitors with novel scaffolds and
deviating modes of binding. Herein we report the design and the short,
high-yielding stereoselective synthesis of a series of chiral, symmetric
pyrrolidine-based inhibitors targeting the open-flap conformation of the
protease. The obtained co-crystal structure with one derivative provides a
valuable starting point for further inhibitor design.
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