I've decided to steer my course of research away from PDT in atherosclerosis, and instead focus on PDT in cancer. My reasoning behind this is two-fold. First, there is not very much information available regarding photoangioplasty since it is such a new application, and second, the feasibility of creating a model system in which I could conduct an experiment is much less than that for cancer. For these reasons I am changing gears and instead focusing on the basic approach of photodynamic therapy and its use in treating cancer.
Three questions immediately come up in regards to PDT, and will predominate my research over the next few weeks. my goal for this week is #1.
1. The main photosensitizer used in PDT is a porphyrin derivative. What is the structure and reactivity of a porphyrin? Why is it so special?
2. How/why does the photosensitizer accumulate in cancer cells?
3. What are the other drugs being investigated for PDT and how do they differ from Hpd?
I plan on this research being a foundation for my Chem 4 experiment.
I reviewed the PDT material I have from Chem 1 and was able to identify several questions that I would like to investigate during my research. This week I will focus on the first and second questions. I intend this research to continue for the rest of the semester, and be the basis of my spring semester project.
1. What is atherosclerosis chemically (other than a calcium build up)? Why does it accumulate, where specifically, and under what conditions?
2. What are the main chemical concepts behind PDT, and how do these pass over to photoangioplasty?
3. How does the PDT drug target the plaque cells? Selective uptake of the drug by abnormal cells? All cells absorb it, but healthy cells excrete it faster?
4. What are some of the current drugs in testing and why?
5. How does the PDT drug prevent reoccurrence/restinosis?
I have decided to finish up my research on epinephrine so that I might focus on a topic that has been of interest to me for a long time: photodynamic therapy (PDT), specifically photoangioplasty. In writing my final epinephrine report however, I am coming up with many more questions that will inevitably be left unanswered. I will make special note of these, and perhaps can return to them at a later date. I'll hand the summary in at our Thursday meeting.
In the meantime, I am also refreshing myself on the PDT literature from Chem 1 and browsing new material on the internet to try to get an idea of where I might want to go with this. I'm not at a point yet where I can identify a drug that I want to investigate. My thought is that I will actually end up working backwards with this research, beginning by learning about atherosclerosis and PDT individually, and eventually making my way to the point where I can combine the two and come up with my own potential drug design that I can then compare to what is out there in clinical trials. For this week though, I plan to finish the epi summary and start investigating atherosclerosis.
A great article for all to read:
Freddolino, Peter L., et al. "Predicted 3D structure for the human B2 adrenergic receptor and its binding site for agonists and antagonists." Proceedings of the National Academy of Sciences. March 2, 2004. 101(9) 2763-2741
This last week was spent learning about the adrenergic receptors of epinephrine. Since epi actually binds to several different receptors, I am focusing on just one of them, the B2 receptor, in order to learn its specific atecholamine, and with what effects? Additionally, I will examine the data produced by the Gaussian calculations I ran last week and look at the HOMO and LUMO.
THIS SOUNDS GOOD BUT YOU MIGHT WANT TO PUT EPINEPHRINE AND THE ADRENERGIC RECEPTORS IN SOME CONTEXT - WHY DID YOU WANT TO LOOK AT THEM IN THE FIRST PLACE? tHERE ARE ADRENERGIC RECEPTORS ALL OVER? WHERE ARE THE ONES YOU ARE INTERESTED IN? WHAT FUNCTIONS DO THEY CONTROL?
My initial investigation was to compare the structures and pathways of epinephrine and albuterol to see how the two differ while still having similar effects on the body. That was a lot to take on, so I focused my interests on learning about the structure of epinephrine and its interaction with Beta-2 receptors specifically. This past week my research focused on learning the basics about the drug. Epinephrine is a unique drug in that it is also naturally occurring in the body. In order to understand how to synthesize and make the injected drug work, I needed to learn how naturally occurring epinephrine works. My questions from last week therefore focused on the following:
1. What is naturally occurring epinephrine?
2. What is the structure of epinephrine?
3. What is its receptor? What are alpha and beta adrenergic receptors?
4. How is epinephrine synthesized in the body?
5. What is the normal pathway of naturally occurring epinephrine in the body?
6. What are the effects of epinephrine in the body?
7. How does injected epinephrine work (direct or indirect interaction with receptors)?
I was able to get a good grasp on these topics. There are two main questions that I would like to focus on this week.
1. How does epinephrine bind to the beta-2 receptor? (Structure of the beta-2 receptor, binding sites)
2. What are the obstacles that injected epinephrine will face in the body prior to reaching its target?