Phenylboronic acid-salicylhydroxamic acid bioconjugates. 2. Polyvalent immobilization of protein ligands for affinity chromatography

Bioconjug Chem. 2001 Mar-Apr;12(2):240-50. doi: 10.1021/bc000086l.

Abstract

Phenylboronic acid bioconjugates prepared from alkaline phosphatase by reaction with either 2,5-dioxopyrrolidinyl 3-[N-[3-(1,3,2-dioxaboran-2-yl)phenyl]carbamoyl]propanoate (PBA-XX-NHS) or 2,5-dioxopyrrolidinyl 6-[[3,5-di-(1,3,2-dioxaboran-2-yl)phenyl]carbonylamino]hexanoate (PDBA-X-NHS) were compared with respect to the efficiency with which they were immobilized on salicylhydroxamic acid-modified Sepharose (SHA-X-Sepharose) by boronic acid complex formation. When immobilized on moderate capacity SHA-X-Sepharose (5.4 micromol of SHA/mL of gel), PDBA-alkaline phosphatase conjugates were shown to be stable with respect to both the alkaline (pH 11.0) and acidic (pH 2.5) buffers utilized to recover anti-alkaline phosphatase during affinity chromatography. Boronic acid complex formation was compared to covalent immobilization of alkaline phosphatase on Affi-Gel 10 and Affi-Gel 15. PDBA-AP.SHA-X-Sepharose was shown to afford superior performance to both Affi-Gel 10 and Affi-Gel 15 with respect to immobilization of alkaline phosphatase, retention of anti-alkaline phosphatase and recovery of anti-alkaline phosphatase under alkaline conditions. High capacity SHA-X-Sepharose (> or = 7 micromol of SHA/mL of gel) was shown to afford superior performance to moderate capacity SHA-X-Sepharose (4.5 micromol of SHA/mL of gel) with respect to stability at pH 11.0 and pH 2.5 when a PDBA-alphaHuman IgG conjugate with a low incorporation ratio of only 1.5:1 was immobilized on SHA-X-Sepharose and subsequently utilized for affinity chromatography of Human IgG. The results are interpreted in terms of either a bivalent or trivalent interaction involving boronic acid complex formation.

MeSH terms

  • Alkaline Phosphatase / chemistry*
  • Alkaline Phosphatase / metabolism
  • Boronic Acids / chemistry*
  • Chromatography, Affinity / methods*
  • Enzyme Stability*
  • Enzymes, Immobilized / chemistry*
  • Horseradish Peroxidase / chemistry
  • Horseradish Peroxidase / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Immunoblotting
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Molecular Structure
  • Protein Binding
  • Salicylamides / chemistry*
  • Sepharose / chemistry*

Substances

  • Boronic Acids
  • Enzymes, Immobilized
  • Immunoglobulin G
  • Salicylamides
  • salicylhydroxamic acid
  • Sepharose
  • Horseradish Peroxidase
  • Alkaline Phosphatase
  • benzeneboronic acid