Non-conservative surface decoration of hemoglobin: Influence of neutralization of positive charges at PEGylation sites on molecular and functional properties of PEGylated hemoglobin

Dongxia Li, Tao Hu, Belur N. Manjula, Seetharama A. Acharya

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

High hydrodynamic volume, high viscosity and high colloidal osmotic pressure (COP) of PEGylated hemoglobin (Hb) have been suggested to neutralize the vasoactivity of acellular Hb. Consequences of non-conservative PEGylation (positive charge of the amino groups at the PEGylation sites is neutralized) using succinimidyl-ester of propionic acid PEG5K on the properties of PEGylated Hb have now been investigated. Non-conservative PEGylation of Hb leads to a much higher increase in the COP and viscosity of Hb than conservative extension arm facilitated (EAF) PEGylation of Hb. Introduction of αα-fumaryl crosslinking decreased the COP of non-conservative PEGylated Hb by stabilization of interdimeric interactions. Compared to the EAF-PEGylated αα-fumaryl Hb, non-conservative PEGylated product shows a comparable COP and higher viscosity. Conservative PEGylation of αα-fumaryl Hb by reductive alkylation chemistry does not increase the COP to this level, but enhanced the molecular volume and viscosity comparable to EAF-PEGylated product. Thus, the molecular properties of PEGylated Hb can be fine tuned using different PEGylation platforms and provide a unique opportunity for the design of second generation PEGylated Hbs.

Original languageEnglish (US)
Pages (from-to)1395-1401
Number of pages7
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1784
Issue number10
DOIs
StatePublished - Oct 1 2008

Keywords

  • Acylation chemistry
  • Blood substitute
  • Colloidal osmotic pressure
  • Hemoglobin
  • PEGylation

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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