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PDBsum entry 2zzu
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Hydrolase/blood clotting
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PDB id
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2zzu
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Contents |
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142 a.a.
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254 a.a.
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191 a.a.
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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 peptidomimetic factor viia inhibitors.
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Authors
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T.Shiraishi,
S.Kadono,
M.Haramura,
H.Kodama,
Y.Ono,
H.Iikura,
T.Esaki,
T.Koga,
K.Hattori,
Y.Watanabe,
A.Sakamoto,
K.Yoshihashi,
T.Kitazawa,
K.Esaki,
M.Ohta,
H.Sato,
T.Kozono.
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Ref.
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Chem Pharm Bull (tokyo), 2010,
58,
38-44.
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PubMed id
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Abstract
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Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as
a promising target for developing new anticoagulant drugs. In previous reports,
we described a S3 subsite found in the X-ray crystal structure of compound 2
that bound to FVIIa/soluble tissue factor (sTF). Based on the X-ray crystal
structure information and with the aim of improving the inhibition activity for
FVIIa/TF and selectivity against other serine proteases, we synthesized
derivatives by introducing substituents at position 5 of the indole ring of
compound 2. Among them, compound 16 showed high selectivity against other serine
proteases. Contrary to our expectations, compound 16 did not occupy the
S3-subsite; X-ray structure analysis revealed that compound 16 improved
selectivity by forming hydrogen bonds with Gln217, Thr99 and Asn100.
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