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PDBsum entry 1ms6
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Design and synthesis of dipeptide nitriles as reversible and potent cathepsin s inhibitors.
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Authors
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Y.D.Ward,
D.S.Thomson,
L.L.Frye,
C.L.Cywin,
T.Morwick,
M.J.Emmanuel,
R.Zindell,
D.Mcneil,
Y.Bekkali,
M.Girardot,
M.Hrapchak,
M.Deturi,
K.Crane,
D.White,
S.Pav,
Y.Wang,
M.H.Hao,
C.A.Grygon,
M.E.Labadia,
D.M.Freeman,
W.Davidson,
J.L.Hopkins,
M.L.Brown,
D.M.Spero,
M.Giradot.
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Ref.
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J Med Chem, 2002,
45,
5471-5482.
[DOI no: ]
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PubMed id
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Abstract
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The specificity of the immune response relies on processing of foreign proteins
and presentation of antigenic peptides at the cell surface. Inhibition of
antigen presentation, and the subsequent activation of T-cells, should, in
theory, modulate the immune response. The cysteine protease Cathepsin S performs
a fundamental step in antigen presentation and therefore represents an
attractive target for inhibition. Herein, we report a series of potent and
reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors
show nanomolar inhibition of the target enzyme as well as cellular potency in a
human B cell line. The first X-ray crystal structure of a reversible inhibitor
cocrystallized with Cathepsin S is also reported.
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