Touria Rguig

08/30/2011

Tr7356

N59, Hemoglobin S

Nucleic Acid Selection against Hemoglobin S to Prevent the Aggregation of Red Blood Cells in Sickle Cell Anemic Patients

Hemoglobin S differs from normal adult hemoglobin called hemoglobin A only by a single amino acid substitution; a valine replacing a glutamine in the 6th position of the beta chain of globin [1]. This single amino acid substitution causes a genetically inherited disease called sickle cell anemia. This disease results in sickle-shaped red blood cells that deliver less oxygen to the body's tissues. These abnormal cells can also get stuck more easily in small blood vessels, and break into pieces that interrupt healthy blood flow.

Valine is a less polar amino acid than glutamate and thus favors hydrophobic interactions between each strand and its neighboring amino acids such as leucine and Histidine [1]. These types of interactions cause the red blood cells to aggregate and become sickled shaped preventing regular blood flow through capillaries and dramatically decreasing the hemoglobin’s high oxygen-binding affinity [1].

Selecting an aptamer against hemoglobin S to inhibit the polymerization of red blood cells caused by valine’s reactivity can prevent the sickling of blood cells. Also, it can potentially restore the high oxygen binding affinity of hemoglobin. Although there are drugs such as “Hydroxyurea” that enhance the quality of life of sickle cell anemic patient, this aptamer could be very specific and causing no detrimental side effects[2].

Specific aim: Synthesis of a specific aptamer that inhibits the aggregation of red blood cells in sickle cell anemic patients.

Hemoglobin can be purchased through Sigma-Aldrich for $204 per 25 mg. The catalog number is H0392-25MG .

References:

1- Lanzkron S, Strouse JJ, Wilson R, et al (June 2008). "Systematic review: Hydroxyurea for the treatment of adults with sickle cell disease". Annals of Internal Medicine 148 (12): 939–55.
2- (2008) Hydroxyurea for Sickle Cell Anemia. New England Journal of Medicine 359:1, 98-99

Here is the link to my proposal: https://docs.google.com/document/d/1so6mZ7vjYMlsYqiFvoKlozjp6_6ktJcX73dZ-vkq9xM/edit?hl=en_US

Here is the link to my progress report: http://aptamerstream.blogspot.com/2011/10/v-behaviorurldefaultvml-o_18.html
Here is a link to my new manuscript: https://docs.google.com/open?id=0By1AdiE2epJ_ZDQzN2E2MTEtZjc1Yy00OTZhLWI1NTgtMjYxY2EzMWU0Mzdl