Abstract

This research proposal describes a program directed towards the total synthesis of the novel anticancer agent calichemicin gamma-1-prime, and a number of its analogs and degradation products. New synthetic technology and strategies for total synthesis are proposed. The design, synthesis and biological investigation of related systems is also a major thrust in this program. Significant contributions to cancer chemotherapy and other biomedical research areas are expected.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA046446-03
Application #
3189718
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1989-09-01
Project End
1991-07-31
Budget Start
1989-09-01
Budget End
1990-07-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
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