Date of Award
Chemistry and Biochemistry
Antibody, DNA, Light chain amyloidosis, Oligonucleotides
Nucleic acids have been found to prevent aggregation as chaperones, as well as act as co-factors and promote aggregation of amyloidogenic proteins leading to various diseases. Immunoglobulin G, IgG, are prone to aggregate as therapeutic proteins, and light chains of IgG can form amyloid fibrils, causing a disease known as light chain amyloidosis. Here we discuss the effect nucleic acids have on full-length immunoglobulin G aggregation. Our results show G-quadruplex DNA, and bulk DNA lead to oligomerization of full-length IgG, and induce increases in secondary structure. Tryptophan fluorescence indicates structural changes are occurring in the presence of DNA. Additionally, IgG oligomers promoted by G-quadruplex DNA are ThT positive. The increase in ThT fluorescence suggests IgG oligomers induced by G-quadruplex DNA are in states similar to amyloid intermediates. To our knowledge, interactions between nucleic acids as potential co-factors and amyloidogenic light chain IgG have not previously been reported. This research reveals interactions between DNA and IgG can occur, leading to the question, do nucleic acids influence amyloid formation of light chain IgG?
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Gomez, Alexa, "Nucleic Acids Promote Oligomerization of Immunoglobulin G" (2021). Electronic Theses and Dissertations. 1926.
Received from ProQuest