HBOCs from Chemical Modification of Hb

Kluger, Ronald; Lui, Francine E.

doi:10.1007/978-3-642-40717-8_10

Cited by 8 publications

(6 citation statements)

References 85 publications

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“…Consequently, a blood alternative, especially a red blood cell (RBC) substitute, is necessary as a medical measure to complement blood transfusion treatment. In the last few decades, hemoglobin (Hb)-based O 2 -carriers (HBOCs) of various kinds, such as glutaraldehyde-polymerized Hb [ 3 – 6 ] and poly(ethyleneglycol)-conjugated Hb (PEG-Hb) [ 7 – 11 ], have been developed [ 12 , 13 ]. However, the practical use of a safe and effective formulation has not been realized [ 3 , 5 , 6 , 12 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters

et al. 2016

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A hemoglobin wrapped covalently by three human serum albumins, a Hb-HSA3 cluster, is an artificial O2-carrier with the potential to function as a red blood cell substitute. This paper describes the synthesis and O2-binding properties of new hemoglobin‒albumin clusters (i) bearing four HSA units at the periphery (Hb-HSA4, large-size variant) and (ii) containing an intramolecularly crosslinked Hb in the center (XLHb-HSA3, high O2-affinity variant). Dynamic light scattering measurements revealed that the Hb-HSA4 diameter is greater than that of either Hb-HSA3 or XLHb-HSA3. The XLHb-HSA3 showed moderately high O2-affinity compared to the others because of the chemical linkage between the Cys-93(β) residues in Hb. Furthermore, the blood circulation behavior of 125I-labeled clusters was investigated by assay of blood retention and tissue distribution after intravenous administration into anesthetized rats. The XLHb-HSA3 was metabolized faster than Hb-HSA3 and Hb-HSA4. Results suggest that the molecular structure of the protein cluster is a factor that can influence in vivo circulation behavior.

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Section: Introductionmentioning

confidence: 99%

Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters

et al. 2016

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“…Since the 1980 s, hemoglobin (Hb)-based O 2 -carriers (HBOCs) of several kinds have been manufactured and evaluated 4 5 6 , such as crosslinked Hb 7 8 , polymerized Hb 9 10 11 , and poly(ethyleneglycol)-conjugated Hb (PEG-Hb) 12 13 14 . Clinical studies of some products reached Phase-III, but side-effects (pressor response) and low efficacy have prevented their practical application 5 10 15 16 .…”

mentioning

confidence: 99%

Safety Evaluation of Hemoglobin-Albumin Cluster “HemoAct” as a Red Blood Cell Substitute

Haruki

Kimura

Iwasaki

et al. 2015

Sci Rep

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A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core–shell structured hemoglobin-albumin cluster designated as “HemoAct”, is an O2-carrier designed for use as a red blood cell (RBC) substitute. This report describes the blood compatibility, hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct has good compatibility with whole blood. Intravenous administration of HemoAct into anesthetized rats elicited no unfavorable increase in systemic blood pressure by vasoconstriction. The half-life of 125I-labeled HemoAct in circulating blood is markedly longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded equivalent values to those observed in the control group with HSA. Histopathologic inspections of the vital organs revealed no marked abnormality in their tissues. All results indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC transfusion.

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“…Studies of RBC substitutes for human use have continued since the 1980s78910. The products with the greatest potential are hemoglobin (Hb)-based O 2 carriers910.…”

mentioning

confidence: 99%

“…The products with the greatest potential are hemoglobin (Hb)-based O 2 carriers910. In the United States, poly(ethyleneglycol)-conjugated Hb111213, polymerized Hb14, intramolecularly cross-linked Hb1516 have been developed and examined in clinical trials7891017181920. Most of these artificial O 2 -carriers are designed to increase molecular size and to avoid renal excretion.…”

mentioning

confidence: 99%

Artificial Blood for Dogs

Yamada

Yokomaku

Kureishi

et al. 2016

Sci Rep

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There is no blood bank for pet animals. Consequently, veterinarians themselves must obtain “blood” for transfusion therapy. Among the blood components, serum albumin and red blood cells (RBCs) are particularly important to save lives. This paper reports the synthesis, structure, and properties of artificial blood for the exclusive use of dogs. First, recombinant canine serum albumin (rCSA) was produced using genetic engineering with Pichia yeast. The proteins showed identical features to those of the native CSA derived from canine plasma. Furthermore, we ascertained the crystal structure of rCSA at 3.2 Å resolution. Pure rCSA can be used widely for numerous clinical and pharmaceutical applications. Second, hemoglobin wrapped covalently with rCSA, hemoglobin–albumin cluster (Hb-rCSA3), was synthesized as an artificial O2-carrier for the RBC substitute. This cluster possesses satisfactorily negative surface net charge (pI = 4.7), which supports enfolding of the Hb core by rCSA shells. The anti-CSA antibody recognized the rCSA exterior quantitatively. The O2-binding affinity was high (P50 = 9 Torr) compared to that of the native Hb. The Hb-rCSA3 cluster is anticipated for use as an alternative material for RBC transfusion, and as an O2 therapeutic reagent that can be exploited in various veterinary medicine situations.

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HBOCs from Chemical Modification of Hb

Cited by 8 publications

References 85 publications

Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters

Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters

Safety Evaluation of Hemoglobin-Albumin Cluster “HemoAct” as a Red Blood Cell Substitute

Artificial Blood for Dogs

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