The Synthesis and Biological Activity of Iron Binding Motifs
Primary Faculty Mentor’s Name
C. Michele Davis McGibony
Proposal Track
Student
Session Format
Paper Presentation
Abstract
Iron is an essential mineral that plays a key role in the oxygen transporting molecule hemoglobin. Iron also helps muscles store and use oxygen. Excess iron in the body can attract electrons, creating harmful oxygen radicals. Iron overload can be caused by several factors such as genetics, age, gender, and having received multiple red blood cell transfusions. Excess iron can lead to many diseases, such as arthritis, liver cirrhosis, heart disease, and several forms of cancer. Iron-chelating therapies work by binding free iron in the bloodstream and by reducing the amount of iron bound in transferrin, the iron transporting molecule. Current iron therapies are time-consuming, painful, and costly. New, more effective chelation therapies are being researched.
The first step in this research is to synthetically produce iron binding motifs modeled after the naturally occurring iron binding protein, adenochrome, which has been isolated from the branchial hearts of Octopus vulgaris. The goals in the synthesis are to produce a chelator with increased water solubility and a higher affinity for chelation of iron. The next step is to test the effectiveness of the synthesized chelators to bind free iron, as well as other first row transition elements, such as chromium, copper, nickel, and aluminum. Evidence has shown that accumulation of aluminum in the body may be involved in the formation of senile plaques, which occur in the brains of patients with Alzheimer’s disease, and is therefore a suspect in the initial cause of the disease. The binding of aluminum could be beneficial in the therapy of early Alzheimer’s patients. Lastly, two types of competition studies will be performed. The first will be to test the ability of the chelator to remove iron from iron-loaded transferrin. The chelators will be exposed to the iron-loaded transferrin and the location of the iron will be detected by first separating the transferrin and the drug using size-exclusion chromatography. The second competition study will be to expose the drug to transferrin and free iron to determine which molecule will bind the iron. Then, the presence of iron in either the drug or transferrin will be tested by using electrophoresis, MALDI-ToF, and we hope to utilize NMR as an additional method for iron detection.
Keywords
Iron, Chelation therapy, Photodynamic therapy
Location
Room 1909
Presentation Year
2014
Start Date
11-15-2014 11:05 AM
End Date
11-15-2014 12:05 PM
Publication Type and Release Option
Presentation (Open Access)
Recommended Citation
Burke, Rachel and Davis McGibony, C. Michele, "The Synthesis and Biological Activity of Iron Binding Motifs" (2014). Georgia Undergraduate Research Conference (2014-2015). 61.
https://digitalcommons.georgiasouthern.edu/gurc/2014/2014/61
The Synthesis and Biological Activity of Iron Binding Motifs
Room 1909
Iron is an essential mineral that plays a key role in the oxygen transporting molecule hemoglobin. Iron also helps muscles store and use oxygen. Excess iron in the body can attract electrons, creating harmful oxygen radicals. Iron overload can be caused by several factors such as genetics, age, gender, and having received multiple red blood cell transfusions. Excess iron can lead to many diseases, such as arthritis, liver cirrhosis, heart disease, and several forms of cancer. Iron-chelating therapies work by binding free iron in the bloodstream and by reducing the amount of iron bound in transferrin, the iron transporting molecule. Current iron therapies are time-consuming, painful, and costly. New, more effective chelation therapies are being researched.
The first step in this research is to synthetically produce iron binding motifs modeled after the naturally occurring iron binding protein, adenochrome, which has been isolated from the branchial hearts of Octopus vulgaris. The goals in the synthesis are to produce a chelator with increased water solubility and a higher affinity for chelation of iron. The next step is to test the effectiveness of the synthesized chelators to bind free iron, as well as other first row transition elements, such as chromium, copper, nickel, and aluminum. Evidence has shown that accumulation of aluminum in the body may be involved in the formation of senile plaques, which occur in the brains of patients with Alzheimer’s disease, and is therefore a suspect in the initial cause of the disease. The binding of aluminum could be beneficial in the therapy of early Alzheimer’s patients. Lastly, two types of competition studies will be performed. The first will be to test the ability of the chelator to remove iron from iron-loaded transferrin. The chelators will be exposed to the iron-loaded transferrin and the location of the iron will be detected by first separating the transferrin and the drug using size-exclusion chromatography. The second competition study will be to expose the drug to transferrin and free iron to determine which molecule will bind the iron. Then, the presence of iron in either the drug or transferrin will be tested by using electrophoresis, MALDI-ToF, and we hope to utilize NMR as an additional method for iron detection.
