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PDBsum entry 1b0e
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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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Inhibition of human neutrophil elastase. 4. Design, Synthesis, X-Ray crystallographic analysis, And structure-Activity relationships for a series of p2-Modified, Orally active peptidyl pentafluoroethyl ketones.
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Authors
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R.J.Cregge,
S.L.Durham,
R.A.Farr,
S.L.Gallion,
C.M.Hare,
R.V.Hoffman,
M.J.Janusz,
H.O.Kim,
J.R.Koehl,
S.Mehdi,
W.A.Metz,
N.P.Peet,
J.T.Pelton,
H.A.Schreuder,
S.Sunder,
C.Tardif.
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Ref.
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J Med Chem, 1998,
41,
2461-2480.
[DOI no: ]
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PubMed id
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Abstract
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A series of P2-modified, orally active peptidic inhibitors of human neutrophil
elastase (HNE) are reported. These pentafluoroethyl ketone-based inhibitors were
designed using pentafluoroethyl ketone 1 as a model. Rational structural
modifications were made at the P3, P2, and activating group (AG) portions of 1
based on structure-activity relationships (SAR) developed from in vitro
(measured Ki) data and information provided by modeling studies that docked
inhibitor 1 into the active site of HNE. The modeling-based design was
corroborated with X-ray crystallographic analysis of the complex between 1 and
porcine pancreatic elastase (PPE) and subsequently the complex between 1 and HNE.
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