Abstract

Libraries of aminoglycosides and mimetics targeting RNA This project will take rational and combinatorial approaches to develop aminoglycosides and mimetics targeting cancer-associated RNA as well as angiogenesis. It will focus on the following programs: 1. We have discovered that 1,3-hydroxyamines are better than the guanidine groups as recognition motif for the complexation of phosphodiesters and the Hoogsteen face of guanosine in RNA. We will use this new motif as a core to develop small-molecule libraries to screen for inhibitors (using surface plasmon resonance) targeting RNAs and integrins associated with cancer and angiogenesis. 2. Attachment of reactive groups or short antisense deoxyoligonucleotides to the lead candidates to develop sequence selective RNA cleaving agents. Significant contributions in the areas of biomedicine, drug design, drug resistance, synthetic organic chemistry and the discovery of a new generation of anti-cancer agents are expected.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA078045-01
Application #
6269919
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
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
Mielgo, Ainhoa; Seguin, Laetitia; Huang, Miller et al. (2011) A MEK-independent role for CRAF in mitosis and tumor progression. Nat Med 17:1641-5
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

Showing the most recent 10 out of 85 publications