Molecule of the Day

Guanine is one of the five aromatic bases that make up the genetic code. They are listed below:

Why would one be more interesting than the others? Well, guanine ends up being the weird one in a bunch of ways…

First of all, it’s not very soluble. Yesterday’s molecule, cyclodextrin, showed some examples of how solubility could modulate things like how poisonous a substance is. Neither of the purines are terribly soluble (the purines are the larger bases; guanine and adenine). One of their metabolites is uric acid. This has terrible solubility as well, and it deposits in the joints in gout. Some animals that have to conserve water will excrete solid urate - birds, for example, and bats. Bat feces — or guano — are rich in both urate and guanine. It is from guano that we get the word guanine.

It’s not just present in diseases and excreta, either! You can use it to make yourself look pretty! Crystals of guanine are really quite beautiful, they refract light in a pearl-like way. They are the compound that makes fish scales look like nothing else. Some spiders have visible guanine as well. Here is an example. I have been told that it’s both a means of storing waste, and adaptive, because it’s a means of changing their appearance. Finally, certain fish actually use guanine crystals as a lens. Finally, guanine is used in cosmetics to give them a glittery color. Shampoos, nail polishes, shimmering lotions — lots of them contain guanine. Ones that don’t tend to contain mica.

These are all examples of Nature taking advantage of a compound’s poor solubility; not many other molecules would work for this since they would dissolve in the ubiquitous water found in all living things. It’s remarkable that something that makes up our DNA has found so many unrelated uses - all of which are a direct function of its poor solubility.

Finally, the more mundane type of guanine (same stuff, just in strands of your DNA) may have another function, as well. Typically, in DNA, you find G paired with C, like this:

G-C Base Pair

If you have a lot of G’s in a sequence of DNA, along with some metal ions (sodium or potassium, usually - these will be present in just about any solution to some extent), your G’s will actually start to bind to each other, and the metal ion:

G-Quartet Structure

These are called G-Quartets. If I’m ordering a strand of DNA from a company that synthesizes it, and it has a lot of G’s in it, I won’t get as much as if it were low in G content (i.e., mostly T, C, and A). This is because these G-quartets form and start messing things up. When you’re synthesizing DNA in a lab, it’s always a single strand (hopefully) - these quartets cause it to pack up.It turns out that these are also probably present in regions of DNA called telomeres. Everyone’s chromosomes have a bunch of “junk DNA” trailing at the end. It’s not useless, though; it’s there because of the way your DNA is copied. The enzymes that do this can’t copy to the very end; they stop a little early. So every time your cells divide, you lose a bit of your telomeres. Eventually, you could run out and die.

Right now, you go long before your telomeres, because people tend to die in much more spectacular fashions involving heart attacks, drugs, cancer, and the like. As medicine gets better and better we may have to worry about such mundane problems as running out of DNA, but right now it’s not very likely to happen to you or your kid. Why do we care, then? Cancers, it turns out, don’t have this telomere problem. They express an enzyme called telomerase that attaches to the the telomeres and synthesizes an extra bit of DNA so they never have to stop dividing.

What does this have to do with guanine? So, we know these telomeres are very G-rich and are likely folding into this quadruplex structure, and we know that you can’t synthesize DNA very well when it’s folded (it works poorly in the lab, not at all in an enzyme), some scientists have taken on these G-quadruplexes as a drug target. The idea is to build a molecule that binds the quadruplex and keeps it from unfolding, thereby preventing telomerase from extending it. After a certain number of divisions, the cancer cells would simply give out. Normal cells have no telomerase so there would be drastically fewer side effects than traditional chemo.

Fecal matter, DNA, nail polish, fish eyes, and a hot anticancer target. Can’t ask for much more from a chemical, I tells ya.

Images generated with CS ChemDraw.