New Classes of Conditional Toxins as Therapeutic Agents Against Breast Cancer.
Abstract
During the first year of support by the grant DAMD17-98-1-8042 (The Idea Grant) we focused on the following projects: (1) Development of sitoxins (signal-regulated, cleavage-mediated toxins). One problem with the earlier design was a significant toxicity of Cup9p. We addressed this by constructing a mutant of Cup9p that does not bind to DNA, thereby greatly reducing the toxicity of Cup9p. Further work on sitoxins using this mutant is under way. (2) To design better portable degrons (degradation signals) for the corn toxin projects (item 3), and also to address the problem described in item 1, we developed a new approach to construct strong degradation signals that consist exclusively of asparagines and lysines. In another advance, we constructed a bivalent inhibitor of the N-end rule pathway. (3) During the first year of this grant, the work on comtoxins began with the construction of a DNA library that expresses polypeptide fragments derived from random segments of the proteins of interest. The current state of this ongoing project is described below.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1999
- Accession Number
- ADA369641
Entities
People
- Alexander J. Varshavsky
Organizations
- California Institute of Technology