Dysinosin A: A Novel Inhibitor of Factor VIIa and Thrombin from a New Genus and Species of Australian Sponge of the Family Dysideidae
File version
Author(s)
Pierens, GK
Fechner, G
de Almeida Leone, P
Ngo, A
Simpson, M
Hyde, E
Hooper, JNA
Bostrom, SL
Musil, D
Quinn, RJ
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
PJ Stang
Date
Size
File type(s)
Location
License
Abstract
A new marine natural product dysinosin A 1 has been isolated from a new genus and species of sponge of the family Dysideidae found near Lizard Island, North Queensland, Australia. Dysinosin A is a potent inhibitor of the blood coagulation cascade factor VIIa and an inhibitor of the serine protease thrombin. Among the distinctive features of dysinosin A are the presence of a 5,6-dihydroxy-octahydroindole-2-carboxylic acid, 3-amino-ethyl 1-N-amidino-?-3-pyrroline, a sulfated glyceric acid, and d-leucine, assembled through three peptidic linkages. Dysinosin A inhibited factor VIIa at a Ki of 108 nM and thrombin at a Ki of 452 nM. The identification of the 1-N-amidino-?-3-pyrroline and 5,6-dihydroxy-octahydroindole-2-carboxylic acid as P1 and P2 moieties respectively, should pave the way for the design and synthesis of new structure-based inhibitors.
Journal Title
Journal of the American Chemical Society
Conference Title
Book Title
Edition
Volume
124
Issue
45
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
© 2002 American Chemical Society. Self-archiving of the author-manuscript version is not yet supported by this publisher. TPlease use the hypertext link above to access the journal's website or contact the author for more information.
Item Access Status
Note
Access the data
Related item(s)
Subject
Chemical sciences
Engineering