Getting A Clue About Cortistatin's Activity | November 2, 2009 Issue - Vol. 87 Issue 44 | Chemical & Engineering News
Volume 87 Issue 44 | p. 27 | Concentrates
Issue Date: November 2, 2009

Getting A Clue About Cortistatin's Activity

Crucial isoquinoline ring in natural product’s structure leads researchers to a set of potential kinase targets for cancer and vision therapies
Department: Science & Technology
Keywords: cortistatin A, kinase inhibitors
Molecular model of cortistatin A (aqua) docked in the X-ray crystal structure of a kinase called ROCK I.
Credit: Adapted from Angew. Chem. Int. Ed.
8744scicon_6
 
Molecular model of cortistatin A (aqua) docked in the X-ray crystal structure of a kinase called ROCK I.
Credit: Adapted from Angew. Chem. Int. Ed.

The natural product cortistatin A is a sought-after target for synthetic chemists because it selectively blocks cellular activities known to be necessary for blood vessel growth. That bioactivity could lead to new therapies for cancers and vision impairments where vessel growth is out of whack. However, the biological targets for cortistatin A and its cortistatin “siblings” have remained elusive. Guided by the knowledge that cortistatin’s isoquinoline ring—which is critical for its activity—is a hallmark of kinase inhibitors, Victor J. Cee and Matthew R. Lee of Amgen; David Y.-K. Chen of Singapore’s Agency for Science, Technology & Research; and K. C. Nicolaou of Scripps Research Institute examined cortistatin A’s affinity for a large panel of kinases (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200904778). They learned that cortistatin A binds tightly to a trio of kinases with a variety of biological roles. Molecular modeling experiments suggest that the isoquinoline ring makes key interactions with the kinases’ ATP binding pockets. However, the team cautions that further work is necessary to link the kinase-binding activity to cortistatin’s potent bioactivity.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

Leave A Comment

*Required to comment