Professor Michael
Gross is a world-reknown expert in the field of mass spectrometry. His research
group in the Department of Chemistry (and the Department of Internal Medicine
at the Medical School) at Washington University uses mass spectrometry to study
protein-ligand interactions and DNA-ligand interactions. A ligand is a molecule
that binds to another molecule and in the case of binding to DNA or a protein,
the ligand binding event usually changes the activity (chemical behavior and
reactivity) of the protein or DNA molecule. Thus, the work that is done in Professor
Gross' lab is important for understanding a number of key biochemical and biophysical
phenomena.
In a study that was recently reported in the Journal of the American Chemical,
Professor Gross' group characterized the binding of metal cations such as K+,
Li+ and Sr2+ to DNA structures. Specifically, they investigated
the binding of these ions to a DNA structure called a Guanine Quadraplex (shown
in Figure 1). These Guanine Quadraplex (G-quadruplex) structures are of interest
because they are localized in a part of the chromosome called the telomere.
Stabilizing these telomeric structures (by binding of ions or other molecules)
makes it harder for the DNA to replicate. Rapid cellular replication (which
requires replication of the DNA) is a hallmark of cancer cells. Cancer cells
grow and divide in an uncontrolled fashion. In their study, Professor Gross'
group determined that the guanine quadraplex appears to bind one or multiple
K+ ions depending on the overall charge of the G-quadruplex. One
strategy to prevent replication of cancer cells might be to design a compound
that binds specifically to this DNA motif.
In this mass spectrometry study, Professor Gross determined the number of K+ ions that bind to the G-quadruplex. Figure 2 shows the mass spectrum of complexes between DNA and potassium ions. Professor Gross concluded that these G-quadruplex structures can bind one or more than one (two, three, or four or more) potassium ions when the total charge on the DNA-potassium complex is -3 or -4 (some of these peaks are labeled in boldtype on Figure 2).
These types of studies are adding to our fundamental understanding of the complex electrostatic interactions in DNA and other biologically important molecules (proteins, RNA, etc.). Electrostatic interactions, as well as other inter- and intramolecular forces will be studied in Chemistry 111.
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Figure 1. The Guanine Quadraplex (G-quadruplex) structure that occurs in telomeric DNA. It consists of 4 guanine bases.
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Figure 2. Mass spectrum of DNA-potassium ionic complexes. The x-axis shows mass-to-charge ratio and the y-axis shows the relative amplitude (RA) of each peak (the amplitude of the highest peak is set equal to 100. The mass-to-charge ratios of a series of peaks that have a total charge = -4 are indicated in bold type on the spectrum. From: J. Amer. Chem. Soc. 125: 42-43 (2003). |