New Classes of Conditional Toxins as Therapeutic Agents Against Breast Cancer

Abstract

During the three-year duration of this grant ((DAMD17-98-1-8042, the Idea Grant), we focused on the following projects: (1) Development of signal-regulated, cleavage-mediated toxins. During this time, we completed the work on the CUP9-mediated, HIV protease-dependent conditional toxins. A paper describing these results has been finished (its completion was delayed by difficulties in some of the necessary control experiments). This paper will be submitted for publication in the Fall of 2001. (2) We also carried out, during the first year of support, an extensive study whose major aim was to construct better portable degrons (degradation signals) that can be used, in particular, for designing conditional toxins. This effort was entirely successful. A paper describing these results was published at the end of 1999 (Suzuki & Varshavsky. Degradation signals in the lysine-asparagine sequence space. EMBO J. 18:6017-6026,1999). A reprint of the paper is enclosed. (3) In 1999, we also completed the construction of a bivalent inhibitor of the N-end rule pathway, a useful reagent for conditional-toxin projects, and published this new approach (Kwon & Varshavsky. Bivalent inhibitor of the N-end rule pathway. J. Biol. Chem. 274:18135-18139, 1999). (4) Other projects that encompass the subject of this grant have also been carried out. They were less successful, given a variety of technical difficulties that we encountered, at the Idea-Grant stage of the work.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2001
Accession Number
ADA394611

Entities

People

  • Alexander Varshavsky

Organizations

  • California Institute of Technology

Tags

DTIC Thesaurus Topics

  • Biomedical And Dental Materials
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Fungi
  • Genetics
  • Medical Personnel
  • Polymer Chemistry
  • Polymeric Films
  • Proteins
  • Proteomics

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Software Engineering
  • Technical Research and Report Writing.

Technology Areas

  • Space