Open AccessApproaches to the Engineering of Hemoglobin‐Based Oxygen Carriers
Author(s) -
Fronticelli Clara,
Bellelli Andrea,
Brinigar William S.
Publication year - 2004
Publication title -
transfusion alternatives in transfusion medicine
Language(s) - English
Resource type - Journals
eISSN - 1778-428X
pISSN - 1295-9022
DOI - 10.1111/j.1778-428x.2004.tb00090.x
Subject(s) - myoglobin , hemoglobin , cooperativity , heme , polymer , blood substitute , oxygen , polymerization , biophysics , hemeprotein , chemistry , biochemistry , medicine , organic chemistry , biology , enzyme
SUMMARY Molecular biology offers the opportunity to construct hemoglobin molecules as blood substitutes tailored to specific therapeutic applications. Oxygen affinity can be manipulated by amino acid substitutions in the heme pocket or on the protein surface. A response to the concentration of plasma‐Cl ‐ that mimics the effect of 2,3‐DPG was also introduced in human Hb. Polymerization of tetrameric Hb prevents the vasoconstriction associated with infusion of Hb solutions. Polymers have been obtained through the formation of intermolecular S‐S bonds between cysteine residues introduced on the Hb surface. In a mouse model, transfusion of polymeric hemoglobins reduced the volume of cerebral infarction. This effect was particularly evident with polymers having a high oxygen affinity (P 50 ≤˜2.0 Torr) and no cooperativity (n = 1). These are the same functional characteristics of myoglobin. Polymers of myoglobin have been constructed and could be a viable alternative to the use of polymeric hemoglobins in some pathological conditions.