Abstract

This grant application describes a program directed at the development of DNA sequence specific molecules by combinatorial molecular imprinting techniques. Appropriately functionalized calicheamicin oligosaccharides with olefinic appendages of various sizes will be allowed to bind into the minor grove of duplex DNA containing two (or more) binding sites, and those who fit will be ligated via the olefin metathesis reaction. Through this and related strategies we hope to develop a series of sequence specific oligosaccharides for certain DNA sequences that can be used as vehicles for specific DNA cleavage and cross-linking as well as for modulating gene expression and suppression as a means to cancer chemotherapy. A second project will involve the construction of an apothilone B library using a combination of solution and solid phase chemistry techniques. The synthesized library will be screened in tubulin polymerization and cytotoxicity assays. Potential anticancer agents are expected to be identified from these studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA078045-01
Application #
6269920
Study Section
Project Start
1998-05-07
Project End
1999-02-28
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
1
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

Gochin, Miriam; Whitby, Landon R; Phillips, Aaron H et al. (2013) NMR-assisted computational studies of peptidomimetic inhibitors bound in the hydrophobic pocket of HIV-1 glycoprotein 41. J Comput Aided Mol Des 27:569-82
Whitby, Landon R; Boger, Dale L (2012) Comprehensive peptidomimetic libraries targeting protein-protein interactions. Acc Chem Res 45:1698-709
Hart, Jonathan R; Liao, Lujian; Yates 3rd, John R et al. (2011) Essential role of Stat3 in PI3K-induced oncogenic transformation. Proc Natl Acad Sci U S A 108:13247-52
Whitby, Landon R; Ando, Yoshio; Setola, Vincent et al. (2011) Design, synthesis, and validation of a ýý-turn mimetic library targeting protein-protein and peptide-receptor interactions. J Am Chem Soc 133:10184-94
Shields, D J; Murphy, E A; Desgrosellier, J S et al. (2011) Oncogenic Ras/Src cooperativity in pancreatic neoplasia. Oncogene 30:2123-34
Murphy, Eric A; Majeti, Bharat K; Mukthavaram, Rajesh et al. (2011) Targeted nanogels: a versatile platform for drug delivery to tumors. Mol Cancer Ther 10:972-82
Hart, Jonathan Ross; Liao, Lujian; Ueno, Lynn et al. (2011) Protein expression profiles of C3H 10T1/2 murine fibroblasts and of isogenic cells transformed by the H1047R mutant of phosphoinositide 3-kinase (PI3K). Cell Cycle 10:971-6
Kolesnichenko, Marina; Vogt, Peter K (2011) Understanding PLZF: two transcriptional targets, REDD1 and smooth muscle ?-actin, define new questions in growth control, senescence, self-renewal and tumor suppression. Cell Cycle 10:771-5
Thomas, Celestine J; Casquilho-Gray, Hedi E; York, Joanne et al. (2011) A specific interaction of small molecule entry inhibitors with the envelope glycoprotein complex of the Junín hemorrhagic fever arenavirus. J Biol Chem 286:6192-200
Sun, Minghao; Hart, Jonathan R; Hillmann, Petra et al. (2011) Addition of N-terminal peptide sequences activates the oncogenic and signaling potentials of the catalytic subunit p110? of phosphoinositide-3-kinase. Cell Cycle 10:3731-9

Showing the most recent 10 out of 85 publications