An investigation of the flexibility and dynamic modes of DNA in solution is proposed. For this purpose, the reactions of various nucleic acids with a series of """"""""oversized"""""""" intercalative ligands (and especially water-soluble mesosubstituted porphyrins) will be considered. These molecules will serve as probes of open regions of DNA that may aid in determining the time range and detailed mechanisms of distortions and dislocations within the helix. Correlations of the relative steric requirements of the ligand molecules with their base pair specificities will be pursued. The experimental findings derived from this research might provide a rational basis for drug design and delivery systems relevant to therapies based upon DNA modification. Porphyrins in general and these derivatives in particular are known to accumulate in tumors. A number of cancer therapies are being developed-based upon porphyrin chemistry; it is thus important to characterize the sequence specificity of these compounds in addition to using them to probe helix dynamics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034676-02
Application #
3286069
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Swarthmore College
Department
Type
Schools of Arts and Sciences
DUNS #
073755381
City
Swarthmore
State
PA
Country
United States
Zip Code
19081
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