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 DNA 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 #
3P41RR001315-16
Application #
6280919
Study Section
Project Start
1998-07-01
Project End
1999-06-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
16
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Los Alamos National Lab
Department
Type
DUNS #
City
Los Alamos
State
NM
Country
United States
Zip Code
87545
Frumkin, Jesse P; Patra, Biranchi N; Sevold, Anthony et al. (2016) The interplay between chromosome stability and cell cycle control explored through gene-gene interaction and computational simulation. Nucleic Acids Res 44:8073-85
Johnson, Leah M; Gao, Lu; Shields IV, C Wyatt et al. (2013) Elastomeric microparticles for acoustic mediated bioseparations. J Nanobiotechnology 11:22
Micheva-Viteva, Sofiya N; Shou, Yulin; Nowak-Lovato, Kristy L et al. (2013) c-KIT signaling is targeted by pathogenic Yersinia to suppress the host immune response. BMC Microbiol 13:249
Ai, Ye; Sanders, Claire K; Marrone, Babetta L (2013) Separation of Escherichia coli bacteria from peripheral blood mononuclear cells using standing surface acoustic waves. Anal Chem 85:9126-34
Sanders, Claire K; Mourant, Judith R (2013) Advantages of full spectrum flow cytometry. J Biomed Opt 18:037004
Cushing, Kevin W; Piyasena, Menake E; Carroll, Nick J et al. (2013) Elastomeric negative acoustic contrast particles for affinity capture assays. Anal Chem 85:2208-15
Houston, Jessica P; Naivar, Mark A; Jenkins, Patrick et al. (2012) Capture of Fluorescence Decay Times by Flow Cytometry. Curr Protoc Cytom 59:1.25.1-1.25.21
Marina, Oana C; Sanders, Claire K; Mourant, Judith R (2012) Effects of acetic acid on light scattering from cells. J Biomed Opt 17:085002-1
Chen, Jun; Carter, Mark B; Edwards, Bruce S et al. (2012) High throughput flow cytometry based yeast two-hybrid array approach for large-scale analysis of protein-protein interactions. Cytometry A 81:90-8
Piyasena, Menake E; Austin Suthanthiraraj, Pearlson P; Applegate Jr, Robert W et al. (2012) Multinode acoustic focusing for parallel flow cytometry. Anal Chem 84:1831-9

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