I need a 6 page research paper on breast cancer but it has to have chemistry-focused points. The medicines used to treat breast cancer; I might suggest choosing one particular medication (or class of

An Example of Choosing and Narrowing a Topic

Let’s start with finding something that interests me. We’ll pretend I want to go into some type of medical field or research. I know someone who has a thyroid issue. I wonder if I can work out my topic to be about thyroid disorders and still keep it chemistry focused.

A few taps on the keyboard and I can find hundreds of thousands if not millions of hits to information about thyroid disorders. So let’s try to narrow that down. Thyroids can be hypoactive, hyperactive or damaged. I’ll pick hyperactive. There’s still a lot of info about hyperactive thyroids, so I’ll choose one aspect of a hyperactive thyroid.

Thyroid Stimulating Hormone (TSH) is a key player in thyroid metabolism, so we’ll start by looking at it. If I go into a little background, I can see that TSH is released by the pituitary gland and tells the thyroid to make more T4 (and T3, which is derived from T4). TSH release is in turn stimulated by TRH, thyrotropin-releasing hormone. OK, we’ve got a nice little pathway there and we know the TSH levels are typically elevated in hyperthyroidism. We could talk about binding mechanisms or the reactions that convert T4 into T3, but I want to look at treatments and maybe pharmaceutical effects. Maybe I’ll change my mind and come back to the chemistry of TSH itself, but let’s look around.

If I look up some medical research, I can see there are several treatments for hyperthyroidism – probably too many to look at all of them, or even one class of them, so I will pick just one and see what I can find about it. One commonly prescribed medicine is Tapazole; that’s the trade name, but I want the generic name of the compound as that is what will be found in the scientific literature. I will look up more about methimazole.

A quick search shows me some basic information about methimazole. If I cut-and-paste from Wikipedia (for my own info and not as part of my paper!), I see:

Thiamazole inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I−) to iodine (I2), hypoiodous acid (HOI), enzyme linked hypoiodate (EOI) facilitating iodine's addition to tyrosine residues on the hormone precursor thyroglobulin, a necessary step in the synthesis of triiodothyronine (T3) and thyroxine (T4).

It does not inhibit the action of the sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors such as perchlorate and thiocyanate.

It acts at CXCL10.

Aha! I now have a wealth of chemically-relevant, basic information that is not too broad in scope. I can start outlining a paper that will talk about how methimazole functions chemically to decrease TSH levels for the treatment of hyperthyroidism. I even have options, based on those three paragraphs.

1. I could talk about the chemical interaction between methimazole and thyroperoxidase and describe the reaction catalyzed by the enzyme and how methimazole works to inhibit it.

2. I could look at the sodium-dependent iodide transporter and describe how it works and then explain how methimazole does not inhibit this protein complex. But that might be a bit stranger to do, since I have to look at how something is either not interacting or interacting but having no effect.

3. Finally, I can look at where exactly methimazole is binding to ‘do its thing’ – in this case, the CXCL10 protein. Looking at this, I think there’s some nice background, but maybe explaining protein inhibition is a different direction than I really want to go. I might keep a tiny bit of this as background and as an example for answering the hydrogen-bonding interaction question I know I will get, but I’ll focus more the reactions in #1.

From here, I can start refining my database searches and learning more about both thyroperoxidase and how methimazole inhibits it. I can describe the chemical reactions (and show my knowledge of organic chemistry reactions and functional groups that I totally have not forgotten). I’ll also have enough background to show why this is important, and maybe add some statistics about hyperthyroidism in my introduction. Finally, I’ll look ahead to try to see where methimazole treatment could be improved. Are there awful side effects that a different drug might not have? Can the efficacy be improved? What’s the next step in treatment?

And there we go. In maybe an hour’s work, I have a good idea of where I want to go with a fairly narrow topic that definitely illustrates principles of chemistry. I’ll have to do some research and read some papers to put together a more detailed outline, but I’m off to a good start to write my paper!

OUTLINE for Methimazole Paper

Topic: Chemical interaction between methimazole and thyroperoxidase and describe the reaction catalyzed by the enzyme and how methimazole works to inhibit it.

Topic Statement

Background

Why is this important? Hyperthyroidism (statistics on population affected, some symptoms)

Methimazole means to control hyperthyroidism

How do we get methimazole?

Mechanism

1. methimazole interacts with thyroperoxidase (paper citation or 2)

   1. describe interaction

   2. describe what thyroperoxidase does on its own

   3. how does methimazole affect thyroperoxidase activity?

2. Binding kinetics?

   1. Reversible reaction? KM and maybe kcat

   2. Position where it binds? Hydrogen bonding interaction or covalent or salt bridge or ?

   3. How does it affect the enzyme? Blocking a site or inducing a conformational change?

3. Metabolites

   1. Thyroperoxidase normally makes ___

   2. Methimiazole slows that down, or makes different product?

   3. What happens to methimazole in the body?

      1. Get excreted?

      2. Degraded?

      3. Half-life

Conclusion

How it works

Future considerations