Date of Award

2021

Document Type

Thesis

Degree Name

M.S.

Department

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.

Provenance

Received from ProQuest

Rights holder

Alexa Gomez

File size

104 pgs

File format

application/pdf

Language

en

Discipline

Biochemistry

Included in

Biochemistry Commons

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