Mass spec and circular dichroism combination can analyze biomolecule chirality

Most biomolecules are chiral. Circular dichroism (CD) spectroscopy is typically used to provide information about that chirality. But the data for mixtures of biomolecules can be difficult to interpret.

Valérie Gabelica, Steven Daly, and Frédéric Rosu of the University of Bordeaux have now combined CD with mass spectrometry to overcome that problem (Science 2020, DOI: 10.1126/science.abb1822). Previous combinations of mass spec and CD were limited to small molecules.

In the new method, the researchers use mass spectrometry to isolate ions of guanine-rich DNA sequences that form structures called G-quadruplexes. They irradiate the DNA with laser pulses of a given wavelength, polarization, and energy. A DNA ion responds to the light by losing an electron, a process that changes the ion’s charge state. The extent of that response will depend on an ion’s chirality and the light’s polarization. The researchers then acquire a mass spectrum of the ions. They switch between different polarizations of light and calculate CD spectra from the intensity of the charge-reduced species as a function of the polarization and wavelength of the light.

The shapes of gas-phase CD spectra of various DNA structures acquired using the new method were similar to conventional solution-phase CD spectra of the same structures, which suggests that the gas- and solution-phase structures have similar base-stacking patterns. Using the new method, the researchers could distinguish between different stacking conformations of the same DNA sequence.

With some tweaks, the new approach should be applicable to proteins too.