CHEM 367: Chemistry Information Retrieval

Brian Leung

Therapeutic effects of Glatiramer Acetate, Copaxone, in Alzheimer's Disease Experiments


My Chem Info Paper

December 3, 2009

GA_hyper.JPG
This is Glatiramer Acetate (GA) made using the sequence blow on hyperchem. Molkal picture will show up soon. I just need a functional picture.


November 29, 2009
Many things have been going on behind the scenes the past few weeks.

Paper is in the process of being written

Outline as Follows:

History of AD
AD Pathology
Glatiramer Acetate
GA in MS/EAE studies
Neurogenesis
Inflammation Response in AD studies
Results of AD Experiments using GA
Discussion

Only problem I am having with is the underlined section, the GA section.
I have a sequence and I found information that GA has an alpha-helix.
AEKYKAKKAKEKAYKKKAKEAKKAKYKAKEAKAYKAEKKAKYAKAKEKAYAKAKEAKAYAKAKAKAEKAKAKAKY
AEKAKAAKYAEKAAKYAEAKAKAAEAK YAAEAKEAAKAAEAKYAAKAEAAKYAAEKAAEKYAKAEAAAEAKEAA

[This seems like the MW would be much larger than the average MW reported from various sources JCB]

November 12, 2009

Assignment 3 (finished)

Found the MW and possible structures of the NEWEST patent for purification and identification of GA's possible structure. Most recent patent.


It's an ALPHA HELIX!

November 10, 2009

Designing the one possible common structure for GA.



MW (g/mol)
Common #
Total g
Lys
146.19
5
730.95
Ala
147.13
3
441.39
Glu
89.09
2
178.18
Tyr
181.19
1
181.19
mw for one subunit
1531.71
Average MW = 4.7-11KDa
Perhaps... 7.85KDa
So probably 5 repeating units.

LYS-LYS-GLU-LYS-TYR-LYS-GLU-LYS-ALA-ALA-ALA

wait... but I don't know the secondary structure...

MW information 2.5kDa to 44kDa (each source has a different MW)
Patent1
Patent 2(this source says more preferable betweek 5KDa)


Molar Ratios:
5lys; 1 ala; 1.5 glu; 1tyr (paragraph 4 )
5lys; 6ala; 2glu; 1tyr (under 11 description )
5-6lys; 2ala; 2glu; 1tyr (Patent1)

mole fraction:
.2-.7 lys;.005-.8ala; .005-.60glu; .005-.3tyr(
Patent 2)

Looking at aa sequence of MBP:
MASQKRPSQRHGSKYLATASTMDHARHGFLPRHRDTGILDSIGRFFGGDRGAPKRGSGKDSHHPARTAHYGSLPQKSHGR
TQDENPVVHFFNIVTPRTPPPSQGKGAEGQRPGFGYGGRASDYKSAHKGFKGVDAQGTLSKIFKLGGRDSRSGSPMARR

Protein Folding of MBP Below:
MBP.jpg
Myelin Basic Protein fron NCBI. From the literature, GA is resembles MBP. Still working on the protein folding.




November 8th, 2009

After looking Dr. Bradley's blogspot , I rethought about my idea. How novel it would be. It would bring up a fun little challenge. I kept all my past information and research that I did with protein tyrosine nitration as it affects tau protein conformation in Alzheimer's Disease.
[Great - it will be fun!]

[Just added a new database on the resource page: **STITCH**
type in glatiramer acetate - looks like some good info about pathways involved JCB]
from FF

Now its the Possible Structure Characterization of Glatiramer Acetate, Copaxone, and its role in Alleviating Alzheimer's Disease Symptoms.

I read into the patent and the pamphlet TEVA Pharmaceuticals provides for healthcare providers as well as patients.
Some Papers:

Review:

Patents:
Patent1
Patent 2

[All of these are important but don't cover the synthesis of the polymer - I would guess that would be patented as well JCB]
[But, the actual synthesis is TEVA Pharm's secret. I just assume hydrolysis reaction. In the patent they mentioned purification, but nothing on exactly how they purified it BPL]




Assignment 2 and other Tau Information

October 24, 2009
Im going to post an article on acawiki.

[Cannot grade - Provide Link JCB] (MY WORK IS ABOVE )


October 23, 2009
I looked up possible papers to use:
-GA used in Multiple Sclerosis OR Alzheimers Disease. Although Alzheimer's disease is much more uncommon, it still provides a similar mechanism that it induces some pathway that deals with microglia.
SO ultimately the question comes down to, do what is more common (MS) or do what is uncommon and more novel (AD)? [If the mechanism of action is similar I don't see why you couldn't include both JCB] {I guess situation is more How to write the paper. Because, the pathway that GA affects is similar in both disease but their pathophysiology of both diseases is different. Furthermore, in GA studies, they are normally done on animals by injecting a foreign protein causing a neuro-immune inflammatory response.}
[I would just start with describing the pathway and see if it makes sense to include both JCB]


October 15, 2009
-read the article, but need to reserach to understand it better.

October 10, 2009
-Found out that Glatiramer Acetate can modulate the immune system by binding to T-Cells Specifically Th1/Th2. I know they release, Interlukin-10, BDNF (Brain Derived Neuro-growth Factor) and in some cases NGF (Neuro Growth Factor), but i cant find any information on its specific binding as in HOW it binds. I tried looking into JBC, PNAS, and also Journal of Neuroscience, but they all didnt give how it bound to the protein receptor's on the extracellular domain. Do you have any suggestions? [That info might not be available - if you collect papers you find on SciFinder on the drug they might actually say that somewhere JCB]
- Also, do you know where i can look for the structure of Glatiramer Acetate? (chem spider was not helpful)
[it is in ChemSpider: http://www.chemspider.com/Chemical-Structure.2339390.html JCB]

October 8, 2009
-signed up for refworks and for my net research. I like my net research a lot.

October 5, 2009
I ve decided to work on neurogenesis by understanding the how neuro and immune systems work together. Im not sure how to narrow it down. I know GA is a molecule involved by immunomodulating. I think ill research how GA specifically interacts with neurons.

So i guess my topic is: The effect of glatiramer acetate on the immuno-nervous system to promote neurogenesis.
[That is a very unusual drug - it should be interesting - start with Wikipedia JCB]

October 3, 2009
- Aricept is a drug commonly used to slow alzheimers disease down. http://www.aricept.com/
[Chemspider should help with info about drugs JCB]

October 1, 2009
-Now im debating whether i should still stick to g quartet... Specifically how the metals play a role in regulation
-what about neurodegeneration, maybe like how it could play a role in the formation of amyloid precursor protein (APP) which would go through proteolytic cleavage that makes amyloid beta (AB) which is the protein that causes Alzheimer disease. Maybe more specifically the signal transduction. (do you have any suggestions?
[Maybe search for Alzheimer therapies with molecules affecting amyloid? JCB] )
-how g-quadruplexes, or G4s, plays a role in HIV?


September 31, 2008
-Found article from naturewith recent info

September 24, 2008:
-Created Wiki, Still thinking of exactly what I want to do my research on.
  • -Thinking about g-quadruplexes...[Excellent starting point - SciFinder/Wikipedia could clarify exactly what you want to cover JCB]**