Hb(alphaalpha,betabeta): a novel fusion construct for a dimeric, four-domain hemoglobin.
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.
Panetta
Gianna
G
Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Università di Roma "Sapienza", Piazzale A. Moro 5 00185 Roma, Italy.
Arcovito
Alessandro
A
Morea
Veronica
V
Bellelli
Andrea
A
Miele
Adriana Erica
AE
D001331:Automation; D001483:Base Sequence; D001802:Blood Substitutes / Q000627:therapeutic use*; D003001:Cloning, Molecular; D017931:DNA Primers; D019281:Dimerization; D015870:Gene Expression; D006441:Hemoglobin A / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D006454:Hemoglobins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D010100:Oxygen / Q000097:blood; D010108:Oxyhemoglobins / Q000627:therapeutic use*; D010957:Plasmids; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use
D001802:Blood Substitutes; D017931:DNA Primers; D006454:Hemoglobins; D010108:Oxyhemoglobins; D011994:Recombinant Proteins; D006441:Hemoglobin A; C020622:hemoglobin B; D010100:Oxygen