Hb(alphaalpha,betabeta): a novel fusion construct for a dimeric, four-domain hemoglobin

Biochim Biophys Acta. 2008 Oct;1784(10):1462-70. doi: 10.1016/j.bbapap.2008.01.003. Epub 2008 Jan 18.

Abstract

Hemoglobin-based blood substitutes are one of the options available to derive a resuscitating fluid taking into account clinical and physiological demands. In this paper we investigated a novel protein, Hb(alphaalpha,betabeta) obtained as a combination of two homodimers alpha(2) and beta(2) both derived from a fusion gene containing two alfa chains or two beta chains, each respectively coupled via a specific linker. The construct here described is thus a novel heterodimeric hemoglobin carrying four heme groups. The protein cannot dissociate into dimers, as demonstrated by its absence of reactivity versus haptoglobin, and is expected to have a relatively long circulating half-life. The modification does not increase the autoxidation rate, but increases the oxygen affinity, due to a destabilization of the T quaternary state. Characterization of the biochemical properties of this protein in comparison with HbA is reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Automation
  • Base Sequence
  • Blood Substitutes / therapeutic use*
  • Cloning, Molecular
  • DNA Primers
  • Dimerization
  • Gene Expression
  • Hemoglobin A / genetics
  • Hemoglobin A / metabolism*
  • Hemoglobin A / therapeutic use
  • Hemoglobins / chemistry
  • Hemoglobins / genetics*
  • Hemoglobins / metabolism
  • Hemoglobins / therapeutic use
  • Humans
  • Kinetics
  • Oxygen / blood
  • Oxyhemoglobins / therapeutic use*
  • Plasmids
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / therapeutic use

Substances

  • Blood Substitutes
  • DNA Primers
  • Hemoglobins
  • Oxyhemoglobins
  • Recombinant Proteins
  • Hemoglobin A
  • hemoglobin B
  • Oxygen