Nucleic Aptamer Selection for Glucagon to Increase Efficiency of Diabetes Diagnosis

John Ferguson
September 16, 2011
Aptamer Fall 2011
Pool: N58, Glucagon, Nucleic Aptamer against Fibrillation of Glucagon


Nucleic Aptamer against Fibrillation of Glucagon

Abstract

Glucagon is a hormone used in emergency situations for people with Diabetes (Jesper 2006). Glucagon raises low blood sugar levels a

nd is specifically used to treat severe Hypoglycaemia. This hormone is usually administered via a syringe when a diabetic individual cannot take sugar by mouth.2 Modern medicine has also used glucagon in diagnosis of the stomach and digestive tract. Glucagon is an important hormone to have in excess for emergences when dealing with low blood sugar but it has been known to cause nausea and vomiting (Kieffer 2000).

An aptamer involved with glucagon would be beneficial to increase its use as a diagnostic medication. Glucagon is used best when administered to patients that have become unconscious from low blood sugar (Schroeder 1984). On the other hand; glucagon is dangerous in the

sense that the patient must be turned on their side to prevent choking if they vomit. An aptamer that can alleviate the symptoms of nausea and vomiting can ultimately increase the diagnostic use of glucagon with Diabetic patients (Dunning 2006). A potential application of this aptamer would be for all Diabetic individuals to counteract Hypoglycaemia by reducing side effects and creating a more practical diagnostic tool when running tests through glucagon. This can be accomplished either through a medication that affects the human body to produce glucagon or through medication with modified glucagon.

Specific Aim 1: The specific aim of this experiment is to find aptamers with high binding affinities to select against glucagon (as seen in Figure 1). This aptamer will need to not only bind to the glucagon molecule but it must affect the way it travels within our blood system in order to decrease its effect to the brain for nausea. This aptamer may also inhibit the shape of the glucagon for a different recognition within the human body. The priority for this experiment is to find an aptamer that binds to the glucagon molecule.


Figure 1: This diagram shows how glucagon can be changed to be a more efficient hormone for drug administration. The specific aim of this experiment is to find aptamers with high binding affinities to select against glucagon.

This experiment will also aim at increasing uses of Glucagon within medical diagnostics. Therefore Glucagon cannot be inhibited in any way that changes its function in the body. Glucagon is available in the -80˚C freezer in the Aptamer Lab. There is 0.5 mg of glucagon for $126.50 and it has been aliquoted and prepared by a student conducting aptamer-glucagon research in the past. The current stock of glucagon is from AnaSpec and their telephone number is 800-452-5530.

Works cited:

(1)"Glucagon - PubMed Health." Web. 30 Aug. 2011. .

(2)"Buy Discount Glucagon Kit - Glucagon Online From a Canadian Drug Store." Canada Pharmacy, Canadian Pharmacy, Canadian Pharmacies, Canada Drugs, Canadian Drugs Online. Web. 30 Aug. 2011. online.aspx>.

(3)"The glucagon-like peptides". Endocr. Rev. 20 (6): 876–913.

Kieffer TJ, Habener JF (2000).

(4)"Localization of the human glucagon gene (GCG) to chromosome segment 2q36----37". Cytogenet. Cell Genet. 38 (1): 76–9.

Schroeder WT, Lopez LC, Harper ME, Saunders GF (1984).

(5)"Alpha cell function in health and disease: influence of glucagon-like peptide-1". Diabetologia 48 (9): 1700–13.

Dunning BE, Foley JE, Ahrén B (2006).


Here is a link to the Final Manuscript:

https://docs.google.com/document/d/1jP1YjdUBZgp420tnwtUHF7mPl0zvGvp9jBIXXjLAG_o/edit?hl=en_US


Here is a link to my full proposal: https://docs.google.com/document/d/11p1epjLDiTbj15VsZB864P9m6EXQftvdjTUCcdpQV-A/edit?hl=en_US&pli=1

10 comments:

Tianlu Ma said...

Good luck with this! It seems like you're going to be doing a lot of assays to make sure that the aptamer binds where it's supposed to.

Shaan said...

Although glucagon is definitely necessary in given situations regardless of if you have diabetes or not, an aptamer that inhibits glucagon activity during diabetes symptoms is actually a really good application. It could kind of be like a treatment for acute symptoms and for emergency purposes. Great work and good look on all the assays!!

Alec Rezigh said...

Interesting idea, John. Just take in mind that for proteins, structure is related to function. It is unlikely that if the structure is changed, the function will remain intact. Best of luck!

Michael Ledbetter said...

Nice work, you may want to flush out more the specifics of glucagon and its aptamer would make a diagnostic test. Also if you are interested specifically in the G receptor of the protein you may want to try and find a peptide of this region. This will allow you to focus on a specific area of your protein while selecting.

Jessica Beardsley said...

I agree with Alec. If you modify the structure of glucagon, would it still be an efficient emergency medication for unconscious diabetics? Even though it might alleviate unwanted symptoms? But I suppose this is research. Besides that, your other points are interesting! Good luck!

Cori Booker said...

This is a really good idea! It's important that therapies are both functional as well as comfortable for patient use. I'm intersted to see how you are planning on complexing the aptamer to a still-functional protein. It might be difficult, but nothing is impossible! Also, you may want to think about how to incorporate some negative selections...

umar.ahmad said...

Pretty interesting target, methodology, and approach to an awesome idea. Best of luck.

Cody Grissom said...

Interesting target, and I love that you are using this for diagnostics. Good luck!

Jeffrey Chang said...

Seems like a tricky task since Glucagon has a variety of functions but very good abstract!

Juan Herrejon said...

Very interesting, John! Seems like you have a solid understanding of the applications of your proposed aptamer! Best of luck in the rounds of selection!