Abstract

This program represents a continuation of a research program in the enediyne area. It includes proposed total syntheses of naturally occurring anticancer agents dynemicin A and maduropeptin chromophore, and designed enediyne conjugates with oligosaccharides, oligonucleotides, and polymeric peptides as targeting agents. The synthetic conjugates will be evaluated for their DNA-sequence specificity (as DNA cleaving agents) and for their cell- and tumor-specificity (as anticancer agents). The proposed research is expected to advance basic knowledge in synthetic, bioorganic, and medicinal chemistry, and may result in the discovery and development of new and selective chemotherapeutic agents for cancer treatment.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA046446-12
Application #
2700410
Study Section
Special Emphasis Panel (ZRG3-BNP (01))
Program Officer
Beisler, John A
Project Start
1989-09-01
Project End
2000-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
12
Fiscal Year
1998
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