Abstract
A novel tetrafunctional reagent, α,γ,α′,γ′-tetra-succinimidyl-hexanediamide-di-glutamate ester (HDG(OSu)4), was successfully synthesized, and a well-defined cross-linked bovine hemoglobin (mainly 128 kDa) was prepared with this reagent. Due to the spatial structure of this cross-linking reagent, the intramolecular and intermolecular cross-linking of bovine hemoglobin was formed simultaneously in one reaction. Although the cross-linked bovine hemoglobin showed a slight decrease in half-saturated O2 pressure value (P50, from 28.1 mm Hg to 21.7 mm Hg) and Hill coefficient (from 2.5 to 2), due to the cross-linkage, it still performed well for O2 delivery.
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References
Chang TMS (1999) Future prospect for artificial blood. Trends Biotechnol. 181: 61-67.
Cheung LC, Storm CB, Gabriel BW, Anderson WA (1984) The preparation of stroma-free hemoglobin by selective DEAE-Cellulose absorption. Anal. Biochem. 137: 481-484.
Keipert PE, Chang TMS (1984) Preparation and in vitro characteristics of a blood substitute based on pyridoxylated polyhemoglobin. Appl. Biochem. Biotechnol. 10: 133-141.
Laemmli UK (1970) Cleavage of structural protein during the assembly of the head of bacteriophage T4. Nature 227: 680-685.
Nelson D, Hai T, Srnak A, Ebeling A, Kunas G, Catarello J, Burhop K (1992) Synthesis and properties of polymerized, diaspirin cross-linked hemoglobins. Biomater. Artif. Cells Immob. Biotechnol. 20: 253-258.
Palaparthy R, Wang H, Gulati A (2000) Current aspects in pharmacology of modified hemoglobins. Adv. Drug Deliv. Rev. 40: 185-198.
Snyder SR, Welty EV, Walder RY, Williams LA, Walder JA (1987) HbXL99 alpha: a hemoglobin derivative that is cross-linked between the alpha subunits is useful as a blood substitute. Proc. Natl. Acad. Sci. USA 84: 7280-7284.
Spahn DR (2000) Current status of artificial oxygen carriers. Adv. Drug Deliv. Rev. 40: 143-157.
Spahn DR, Leone BJ, Reves JG, Pasch T (1994) Cardiovascular and coronary physiology of acute isovolemic hemodilution: a review of nonoxygen-carrying and oxygen-carrying solution. Anesth. Analg. 78: 1000-1021.
Winslow RM (2000) Blood substitutes. Adv. Drug Deliv. Rev. 40: 131-142.
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Yun, Q., He, M., Xing, W. et al. A novel tetrafunctional reagent for simultaneous intramolecular and intermolecular cross-linking of bovine hemoglobin. Biotechnology Letters 26, 1359–1363 (2004). https://doi.org/10.1023/B:BILE.0000045633.36744.0d
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DOI: https://doi.org/10.1023/B:BILE.0000045633.36744.0d