Date of Award
2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biotechnology Science and Engineering
Committee Chair
Carmen Scholz
Committee Member
Bernhard Vogler
Committee Member
Sharifa Love-Rutledge
Committee Member
Olaf Nachtigall
Committee Member
MNV Ravi Kumar
Research Advisor
Carmen Scholz
Subject(s)
Nervous system--Diseases--Genetic aspects, Polymerization, Glutamine
Abstract
The abnormal expansion of poly (L-glutamine) repeats beyond a normal threshold (with disease onset at >35 repeat units) has been linked with several neurodegenerative diseases classified as poly (Q) diseases. To investigate the role of this uncontrolled polyQ expansion in disease onset, it is important to understand the changes that occur when the length of poly (L-glutamine) sequences surpasses the normal threshold. To comprehend the role and behavior of these expanded segments, it is essential to develop synthetic techniques that allow polymer production with controlled length. This ensures the accurate representation of healthy and abnormal poly (L-glutamine) segments. However, a direct synthesis route of this polymer has proven challenging and there is no reported method for synthesizing poly (L-glutamine) with controlled chain lengths. Therefore, the primary focus of this research is to design and develop a robust synthetic protocol for the synthesis of poly (L-glutamine) oligomers with 10 to 50 repeat units. The synthesis of poly(L-glutamine) was achieved through the controlled ring-opening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride initiated by a well-defined initiator. The resulting polymer was deprotected with Trimethylsilyl iodide (TMSI) to generate a free acid that is crucial for the next final amidation step to achieve poly(L-glutamine). The reaction conditions, including monomer-to-initiator ratio, solvent choice, and reaction temperature, were carefully optimized to achieve controlled polymerization. These polymer samples with different lengths will be further characterized to study the biophysical behavior and their relation to polyQ diseases. This research will offer valuable insights into the synthesis and subsequent characterization of well-defined poly(L-glutamine).
Recommended Citation
Singh, Nirupama, "Synthesis of poly (L-glutamine) of controlled chain length : a novel synthetic approach for developing models to study polyQ diseases" (2025). Dissertations. 437.
https://louis.uah.edu/uah-dissertations/437
