Abstract

This proposal outlines seven specific projects which continue our investigation of the shikimic acid biosynthetic pathway. Further work on the synthesis of chiral metabolites will be used to set the stage for detailed studies on several important enzymes in the pathway. These enzymes include chorismate mutase, anthranilate synthase, PABA synthase, and 3-dehydroquinate synthase. The design of inhibitors of these enzymes is also an important objective. Such inhibitors may serve as the prototypes for new experimental antibiotics possessing little or no host toxicity, since these enzymes are not found in mammalian metabolism. This work will also have important bearing on herbicide research.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM024054-08
Application #
3272048
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1978-01-01
Project End
1986-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Cornell University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850

  Publications

Dodge, Hiroko H; Ybarra, Oscar; Kaye, Jeffrey A (2014) Tools for advancing research into social networks and cognitive function in older adults. Int Psychogeriatr 26:533-9
Ganem, Bruce (2009) Strategies for innovation in multicomponent reaction design. Acc Chem Res 42:463-72
Fan, Lijun; Adams, Ashley M; Polisar, Jason G et al. (2008) Studies on the chemistry and reactivity of alpha-substituted ketones in isonitrile-based multicomponent reactions. J Org Chem 73:9720-6
Zhang, Sheng; Wilson, David B; Ganem, Bruce (2003) An engineered chorismate mutase with allosteric regulation. Bioorg Med Chem 11:3109-14
Joseph, Erin; Eiseman, Julie L; Hamilton, Diana S et al. (2003) Molecular basis of the antitumor activities of 2-crotonyloxymethyl-2-cycloalkenones. J Med Chem 46:194-6
Chen, Shuqing; Vincent, Sarah; Wilson, David B et al. (2003) Mapping of chorismate mutase and prephenate dehydrogenase domains in the Escherichia coli T-protein. Eur J Biochem 270:757-63
Hamilton, Diana S; Zhang, Xiyun; Ding, Zhebo et al. (2003) Mechanism of the glutathione transferase-catalyzed conversion of antitumor 2-crotonyloxymethyl-2-cycloalkenones to GSH adducts. J Am Chem Soc 125:15049-58
Hamilton, Diana S; Ding, Zhebo; Ganem, Bruce et al. (2002) Glutathionyl transferase catalyzed addition of glutathione to COMC: a new hypothesis for antitumor activity. Org Lett 4:1209-12
Vincent, Sarah; Chen, Shuqing; Wilson, David B et al. (2002) Probing the overlap of chorismate mutase and prephenate dehydrogenase sites in the escherichia coli T-protein: a dehydrogenase-selective inhibitor. Bioorg Med Chem Lett 12:929-31
Zhang, Qingrong; Ding, Zhebo; Creighton, Donald J et al. (2002) Alkylation of nucleic acids by the antitumor agent COMC. Org Lett 4:1459-62

Showing the most recent 10 out of 20 publications