Doctoral Dissertations

Keywords and Phrases

Amyloid fibrils; Glycosylation; Insulin Fragments; Protein Stability


“The stability of a protein-based biological drug is an important concern during processing, storage or patient administration. There are various forces which contribute to the stabilizing of proteins. Both hydrogen bonds and hydrophobic interactions play an important role in protein stability. Improper folding or misfolding of proteins leads to aggregation, which is a major problem found in the bioprocessing industry. The objectives of this research are: 1) to determine the effect of environmental factors such as pH, temperature, additives or salts, and cosolvents on the stability human serum albumin (HAS), which is the most abundant protein in plasma, 2) to determine the effect of environmental factors on the propensity to aggregate of insulin fragments, and 3) to determine the effect of post-translational modifications such as glycosylation on the propensity to aggregate of insulin fragments. Small-Angle Neutron Scattering (SANS) was used to explore the effect of environmental factors on the intra and inter molecular interactions of HSA. The effect of cosolvents, pH and temperature on the protein conformation and on protein-protein interactions was explored. The propensity to aggregate, particularly the propensity to form amyloid fibrils of the region of the insulin A-chain (where amino acid sequence for bovine and human insulins is different) was then studied. Aggregation was monitored by fluorescence and infrared spectroscopy and optical microscopy. Both fragments formed fibrils at pH 1.6 and a temperature of 60°C. These peptides were glycosylated with D-glucose by the Maillard reaction to increase their stability. Glycosylated peptides were highly stable and they did not show signs of fibril formation during the course of the experiment”--Abstract, page iv.


Forciniti, Daniel

Committee Member(s)

Ludlow, Douglas K.
Barua, Dipak
Liang, Xinhua
Westenberg, David J.


Chemical and Biochemical Engineering

Degree Name

Ph. D. in Chemical Engineering


This work was supported by a grant from the Whitaker Foundation. The research at Oak Ridge was supported by the Division of Materials Sciences, U.S. Department of Energy under contract No. DE-AC05-96OR22464 with Lockheed Martin Energy Research Corp.

The work done on this project was funded in part by the National Science Foundation (CBET 0933468).


Missouri University of Science and Technology

Publication Date

Summer 2020

Journal article titles appearing in thesis/dissertation

  • Effect of methanol and glycerol on the structure of human serum albumin solutions
  • Effect of differences in the primary structure of the a-chain on the aggregation of insulin fragments
  • Effect of glycosylation on the aggregation of insulin A-chain fragments


xvii, 138 pages

Note about bibliography

Includes bibliographic references.


© 2020 Paul Praveen Nakka, All rights reserved.

Document Type

Dissertation - Open Access

File Type




Thesis Number

T 11753

Electronic OCLC #