(Principal Investigator's) The overall goals of this program are: (i) The development of advances in strategy and the discovery of enabling reactions of value in organic synthesis and (ii) the application of these findings to advance human health. While we continue our long term interest in the synthesis of naturally occurring antiinfectious agents, we also include cytotoxic antitumor agents, particularly where a novel mechanism of action has been inferred. Moreover, in this program we continue our quest to develop and evaluate new vaccine constructs to foster immunity against tumorgenesis and metastasis. Among the specific goal structures that we will attempt to synthesize are (i) class of marine derived natural products which can be classified as the eleuthesides (including eleutherobin, sarcodictyn and valdivone A) (eleutherobin has a demonstrated taxol like effect on the rate of microtubulin depolymerization), (ii) heliquinomycin and related structures such as rubromycin and purpuromycin (heliquinomycin is the first reported inhibitor of DNA helicase), (iii) saframycin B, an antibiotic with potent action against gram positive bacteria, (iv) yaoundamine B which is a potent antimalarial agen and (v) frondosin which is a potent PKC inhibitor and an inhibitor of IL-8 receptors. In addition, (vi) we continue our work on the design, synthesis and evaluation of new second and third generation constructs for evaluation as anticancer vaccines. The scope of this inquiry includes lipid conjugates to replace (or augment) KLH, clustered presentations to mimic antigen as presentations in mucins, and antigen analogs in the hope of triggering more aggressive immune responses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI016943-23
Application #
6372981
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Tseng, Christopher K
Project Start
1980-03-01
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
23
Fiscal Year
2001
Total Cost
$403,459
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
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Gaul, Christoph; Njardarson, Jon T; Danishefsky, Samuel J (2003) The total synthesis of (+)-migrastatin. J Am Chem Soc 125:6042-3
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