A number of new bis-intercalating anthracycline antibiotics, analogs of daunomycin, have been designed and synthesized in our collaborator's laboratory. The rational design of these new compounds was based upon the geometry of monomeric anthracyclines bound to DNA oligonucleotides observed in high-resolution crystal structures. Monomeric units of daunorubicin have been linked through their reactive 3' NH2 substituents on the daunosamine moieties to form these bisanthracyclines. Since differential intracellular binding complexes can be distinguished and quantitated by fluorescence lifetime analyses, we will use this approach to detect binding of these new agents to different subcellular components. From such determinations those drug complexes responsible for cytotoxicity may be ascertained. The design of new potential anticancer agents based on known structural principles and binding properties can be used to produce a compound with significantly increased D NA binding affinity and with interesting biological activity.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001315-19
Application #
6470671
Study Section
Project Start
2001-07-01
Project End
2002-06-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
19
Fiscal Year
2001
Total Cost
$121,168
Indirect Cost
Name
Los Alamos National Lab
Department
Type
DUNS #
City
Los Alamos
State
NM
Country
United States
Zip Code
87545
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