Abstract

This program is directed towards the development of new synthetic technology and strategies relating to the enediyne anticancer agents calicheamicin gamma1 l and dynemicin A. The developed methodology will be applied to the total synthesis of the natural products themselves and to the design, synthesis and biological evaluation of a number of related model compounds. It is anticipated that the proposed work will have significance in the areas of organic synthesis, biomedical research, and cancer chemotherapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA046446-07
Application #
3189717
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1989-09-01
Project End
1996-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Tan, Chalet; de Noronha, Rita G; Devi, Narra S et al. (2011) Sulfonamides as a new scaffold for hypoxia inducible factor pathway inhibitors. Bioorg Med Chem Lett 21:5528-32
Nicolaou, K C (2009) Inspirations, discoveries, and future perspectives in total synthesis. J Org Chem 74:951-72
Narita, Takuhito; Yin, Shaoman; Gelin, Christine F et al. (2009) Identification of a novel small molecule HIF-1alpha translation inhibitor. Clin Cancer Res 15:6128-36
LaMarr, W A; Yu, L; Nicolaou, K C et al. (1998) Supercoiling affects the accessibility of glutathione to DNA-bound molecules: positive supercoiling inhibits calicheamicin-induced DNA damage. Proc Natl Acad Sci U S A 95:102-7
Liu, C; Smith, B M; Ajito, K et al. (1996) Sequence-selective carbohydrate-DNA interaction: dimeric and monomeric forms of the calicheamicin oligosaccharide interfere with transcription factor function. Proc Natl Acad Sci U S A 93:940-4
Wrasidlo, W; Hiatt, A; Mauch, S et al. (1995) In vivo efficacy of novel synthetic enediynes 1. Acta Oncol 34:157-64