TBPP_base fractionation of blood plasma
TBPP_base fractionation of blood plasma
TBPP_base fractionation of blood plasma
Kartei Details
Karten | 15 |
---|---|
Sprache | English |
Kategorie | Chemie |
Stufe | Universität |
Erstellt / Aktualisiert | 28.12.2016 / 03.01.2017 |
Lizenzierung | Keine Angabe |
Weblink |
https://card2brain.ch/box/20161228_tbppbase_fractionation_of_blood_plasma
|
Einbinden |
<iframe src="https://card2brain.ch/box/20161228_tbppbase_fractionation_of_blood_plasma/embed" width="780" height="150" scrolling="no" frameborder="0"></iframe>
|
recovered: blood collection for red cells and platelets, plasma as by-product. Source plasma: dedicated plasma collection by plasmapheresis
WW II created medical need. Navy contracted with Harvard to identify and isolate transfusible substance from blood.
leads Harvards efforts, investigated solubility of proteins, father of plasma fractionation, saved thousands of lifes
differential solubility of plasma proteins in alcoholic solutions. Protein solubility controlled by: alcohol concentration, pH, temperature, ionic strength, protein concentration
3 of 5 primary process parameters (EtOH, temp., pH) are directly manipulated in the process, the others indirectly via reagent additions, separation into several fractions enriched in specific proteins, temp. Maintained to solution freezing to minimize denaturation, avoid extreme local conditions because of denaturation
5 fractions from solutions of increasing EtOH concentrations. 10 fractionation schemes: Cohn Method 6 (IgG paste and albumin), Oncley Method 9 (IgG purification). Cohn method: pioneering work, first industrial scale manufacture infusible albumin, basis for other processes, side fractions used for gain of other proteins, variations possible. Precipitate 2 and 3: IgG, precipitate 4: albumin. Kistler Nitschmann method: modification of Cohn Method 10, purity comparable to the other method, increased recoveries (+50%) and smaller process, still in use at CSL for albumin, IVIG, IgG paste
number of plasma proteins: 1980-2014, from 100 to 10'546 proteins. 10 proteins constitute 90% of protein mass / 75% of revenues generated with 4 proteins: albumin, IgG, Factor 8, AAT. Wide concentration rate. Plasma proteins as biotherapeutics: structure and biological activity to be preserved. At industrial scale: precipitation and biochromatography. add precipitant --> centrifugation --> chromatography
depends on distribution of hydrophilic and hydrophobic AS residues on proteins surface. Hydrophobic: predominantly in the core, proteins with high hydrophobic AS content on surface have low solubility. Charged and polar surface: interactions with ionic groups in aqueous solutions and increase solubility. Hydration layer: interaction of protein surface with surrounding water (H-bonding and dipol-dipol) lead to hydration shell, essential for proteins solvation and biological function.