Purification of α2-macroglobulin from Cohn Fraction IV by immobilized metal affinity chromatography: A promising method for the better utilization of plasma

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jul 1:1025:68-75. doi: 10.1016/j.jchromb.2016.05.013. Epub 2016 May 10.

Abstract

As an abundant plasma protein, α2-macroglobulin (α2-M) participates widely in physiological and pathological activities including coagulation regulation, antitumor activities, and regulation of cytokines. It also presents a therapeutic potential for radiation injury. A two-step isolation method for the purification of α2-M from Cohn Fraction IV is described. This process includes a salting-out method and immobilized metal affinity chromatography. The LC-ESI-MS/MS analysis and a comparison of the amino acid composition demonstrated that the final product was α2-M. The final protein, with a purity of approximately 95% and a yield of nearly 45%, was obtained from Cohn Fraction IV regardless of plasma haptoglobin type, although all but type 1-1 have previously been considered unfavorable for α2-M preparation. The effects of temperature, pH, and methylamine on α2-M activity were evaluated to avoid activity loss during preparation and preservation. The results suggested that α2-M activity could be readily inactivated at temperatures above 50°C, at pH levels above 9.0 or below 4.0, or in the presence of methylamine. Cohn Fraction IV is usually discarded as a biological waste product in the human serum albumin production process; because the simple process developed in this study is relatively inexpensive, the preparation of α2-M from Cohn Fraction IV may better utilize human plasma, a valuable resource.

Keywords: Better utilization of plasma; Cohn fraction IV; Immobilized metal affinity chromatography; Plasma derivatives; α2-macroglobulin.

MeSH terms

  • Blood Proteins / chemistry*
  • Chromatography, Affinity / methods*
  • Humans
  • Hydrogen-Ion Concentration
  • Methylamines
  • Tandem Mass Spectrometry
  • Temperature
  • alpha-Macroglobulins / analysis
  • alpha-Macroglobulins / chemistry
  • alpha-Macroglobulins / isolation & purification*

Substances

  • Blood Proteins
  • Cohn fraction IV
  • Methylamines
  • alpha-Macroglobulins
  • methylamine