Many anti-cancer drugs bind to DNA, unwinding the double helix and changing the degree of rotation between nucleotides. This technology uses second harmonic generation spectroscopy to measure the relative orientation of a pair of DNA-binding molecules. Second harmonic generation, an optical process, gives a beam with twice the frequency of a laser light source. The intensity of this second harmonic can be measured to reflect the electric field interference's dependence on a sample's molecular orientation. Understanding the degree to which a drug unwinds DNA would provide a more complete molecular understanding of DNA-binding drug action. This technology can be to screen for and investigate DNA-binding drug candidates.
Understanding DNA unwinding in an in vitro environment enables rational design of more effective anti-cancer drugs.
Unlike conventional techniques to isolate molecular structures, such as crystallography, this technology has the capacity to acquire data in a solution more closely resembling DNA environment in vivo. Measuring important properties of DNA-binding drug candidates in a simulated natural environment gives an improved understanding of double helix unwinding and consequently the design of more effective anti-cancer drugs.
In vitro data has demonstrated DNA attachment to colloidal microparticles.
Lead Inventor:
Kenneth Eisenthal, Ph.D.
Applications:
- Screen the effects of DNA-binding compounds on DNA unwinding.
- Probe basic structural features of biochemical complexes for the study of structural biology.
- Provide information on other potential structural changes induced by drug binding distinct from DNA unwinding, such as kinking or supercoiling.
- Use as a general DNA binding assay if SHG intensity reproducibly changes when a compound binds to DNA.
Advantages:
- Measures drug-induced DNA unwinding.
- Acquires data in solution more closely mimicking the DNA environment in vivo.
- Improves research and development of new DNA-binding drug candidates.
Patent information:
Patent Pending
Tech Ventures Reference: IR CU13153
Related Publications:
- J. Liu, M. Subir, K. Nguyen, K.B. Eisenthal. Second harmonic studies of ions crossing liposome membranes in real time. The Journal of Physical Chemistry B Letters. Vol. 112, 2008, pp.15263-15266.
- B. Doughty, S.W. Kazer, K.B. Eisenthal. Binding and cleavage of DNA with the restriction enzyme EcoR1 using time-resolved second harmonic generation. PNAS. Vol. 108, Issue 50, Dec. 2011, pp. 19979-19984.
- B. Doughty, Y. Rao, S.W. Kazer, S.J.J. Kwok, N.J. Turro, K.B. Eisenthal. Binding of the anti-cancer drug Daunomycin to DNA probed by second harmonic generation. The Journal of Physical Chemistry B. Article ASAP, Feb. 2013.
- B. Doughty, Y. Rao, S.W. Kazer, S.J.J. Kwok, N.J. Turro, K.B. Eisenthal. Probing the relative orientation of molecules bound to DNA through controlled interference using second-harmonic generation. PNAS. Vol. 110, Issue 15, Apr. 2013, pp.5756-5758.