Mechanistic Insights into Protein Stability, Aggregation, and Rheological Changes through Dynamic Light Scattering/Raman Spectroscopy and Microcapillary Viscometry(PPT)

摘要

1. Combination of SEC-MALLS, DLS-Raman, Microcapillary Viscometry together with mathematical models on aggregation allows detailed understanding of protein stability, aggregation mechanisms and viscosity evolution. This allows the development of formulation design rules. 2. aCgn at low pH ranges undergoes thermal induced aggregation primarily through chain polymerization. Higher Mw and larger size aggregates forming at the higher pH’s investigated. 3. For the range of pH investigated, nucleation time, n, is orders of magnitude slower then growth time, g, -this indicates rapid growth compared to slow nucleation. This is further enhanced at higher pH 4. With increasing aggregation there is an increase in -sheet and decrease in -helix. The hydrogen bonding environment also changes. 5. Viscosity enhancement during aggregation cannot be explained by Mw alone. Good correlation seen with -sheet increase. This maybe due to impact of -sheet on persistance length, and therefore flexibility of formed filaments (focus of on-going study)