Identification of Inhibitors of FXII

Bensel, Alexandra C. (2016) Identification of Inhibitors of FXII. Undergraduate thesis, under the direction of Ziaeddin Shariat-Madar from Pharmacology , University of Mississippi.

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Abstract

Hereditary angioedema is characterized by recurrent swelling of the extremities, larynx, and gastrointestinal tract. While type I and type II hereditary angioedema result from a C1-inhibitor deficiency, a new variant of the disease, type III hereditary angioedema, was recently discovered in individuals with functioning levels of the C1-inhibitor. Ongoing research has postulated that increased activity of factor XII is responsible for this new form of hereditary angioedema because it causes overproduction of bradykinin. The purpose of the experiment was to identify inhibitors of factor XII. One hundred and seventy six molecules were screened through a dose response using Human Factor alpha-XIIa as the enzyme and 4nM S2302 as the substrate, while incubated in HEPES-carbonate buffer. The molecules were chosen from The University of Mississippi National Center for National Products Research after being extracted from plants exhibiting anti-inflammatory properties. Seven compounds inhibited factor XII at concentrations ranging from 0.03 to 10nM. After multiple assays, three compounds from Plate NCNPR-XTL-036:Daughter showed a significant decrease in FXII activity. B7, E2, and H7 were identified to be inhibitors of FXII.

Item Type: Thesis (Undergraduate)
Creators: Bensel, Alexandra C.
Student's Degree Program(s): B.S. in Pharmaceutical Sciences
Thesis Advisor: Ziaeddin Shariat-Madar
Thesis Advisor's Department: Pharmacology
Institution: University of Mississippi
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
R Medicine > R Medicine (General)
R Medicine > RS Pharmacy and materia medica
Depositing User: Alexandra Bensel
Date Deposited: 03 Jun 2016 19:35
Last Modified: 03 Jun 2016 19:35
URI: http://thesis.honors.olemiss.edu/id/eprint/699

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