Abstract |
Kalata B1 is a plant protein with remarkable thermal, chemical and enzymatic stability. Its potential applications could be centered on the possibility of using its cyclic structure and cystine knot motif as a scaffold for the design of stable pharmaceuticals. To discover potent dengue NS2B-NS3 protease inhibitors, we have prepared various kalata B1 analogues by varying the amino acid sequence. Mass spectrometric and biochemical investigations of these analogues revealed a cyclopeptide whose two fully oxidized forms are substrate-competitive inhibitors of the dengue viral NS2B-NS3 protease. Both oxidized forms showed potent inhibition with K(i) of 1.39+/-0.35 and 3.03+/-0.75 microM, respectively.
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Authors | Yaojun Gao, Taian Cui, Yulin Lam |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 18
Issue 3
Pg. 1331-6
(Feb 2010)
ISSN: 1464-3391 [Electronic] England |
PMID | 20042339
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright (c) 2009 Elsevier Ltd. All rights reserved. |
Chemical References |
- Cyclotides
- Disulfides
- NS2B protein, flavivirus
- Serine Proteinase Inhibitors
- Viral Nonstructural Proteins
- kalata B1
- NS3 protease, dengue virus
- Serine Endopeptidases
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Topics |
- Amino Acid Sequence
- Cyclotides
(chemistry)
- Dengue
(drug therapy)
- Dengue Virus
(enzymology)
- Disulfides
(chemistry)
- Drug Design
- Molecular Sequence Data
- Serine Endopeptidases
(metabolism)
- Serine Proteinase Inhibitors
(chemistry, isolation & purification, pharmacology)
- Viral Nonstructural Proteins
(metabolism)
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