Date of Award
2021
Document Type
Masters Thesis
Degree Name
M.S.
Organizational Unit
College of Natural Science and Mathematics, Chemistry and Biochemistry
First Advisor
Scott Horowitz
Second Advisor
Martin Margittai
Third Advisor
Brian Majestic
Fourth Advisor
Erich Chapman
Fifth Advisor
Erich Kushner
Keywords
Antibody, DNA, Light chain amyloidosis, Oligonucleotides
Abstract
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?
Publication Statement
Copyright is held by the author. User is responsible for all copyright compliance.
Rights Holder
Alexa Gomez
Provenance
Received from ProQuest
File Format
application/pdf
Language
en
File Size
104 pgs
Recommended Citation
Gomez, Alexa, "Nucleic Acids Promote Oligomerization of Immunoglobulin G" (2021). Electronic Theses and Dissertations. 1926.
https://digitalcommons.du.edu/etd/1926
Copyright date
2021
Discipline
Biochemistry