We propose to explore the potential of human and bovine hemoglobins as oxygen carriers for transfusional fluids.
The aim i s to obtain highly purified indissociable tetramers of the two hemoglobins with an oxygen affinity compatible with oxygen transport in vivo. The research will involve the development of the necessary compounds, full analyses of their physico-chemical and functional properties, and initial testing of their storage stability and retention time in small animals. One-step chemical reactions will be used for obtaining the desired hemoglobin derivatives, using limited and specific chemical modifications, so as to avoid formation of products with high antigenic activity. Two compounds already obtained by cross-linking bovine hemoglobin with bis-dibromosalicyl-fumarate will be extensively purified and analyzed for their functional properties and sites of cross-links. New treatments will be designed for human hemoglobin whose cross-linked products have an oxygen affinity higher than that desirable in transfunctional fluids.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL033629-01A1
Application #
3345699
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Fronticelli, C; Brinigar, W S; Olson, J S et al. (1993) Recombinant human hemoglobin: modification of the polarity of the beta-heme pocket by a valine67(E11)-->threonine mutation. Biochemistry 32:1235-42
Gryczynski, Z; Bucci, E; Kuyyba, J (1993) Linear dichroism study of metalloporphyrin transition moments in view of radiationless interactions with tryptophan in hemoproteins. Photochem Photobiol 58:492-8
Bucci, E; Fronticelli, C; Gryczynski, Z et al. (1993) Effect of intramolecular cross-links on the enthalpy and quaternary structure of the intermediates of oxygenation of human hemoglobin. Biochemistry 32:3519-26
Gryczynski, Z; Bucci, E (1993) A new front-face optical cell for measuring weak fluorescent emissions with time resolution in the picosecond time scale. Biophys Chem 48:31-8
Chiancone, E; Fronticelli, C; Gattoni, M et al. (1992) Immobilized hemoglobin in the purification of hemoglobin-based oxygen carriers. J Chromatogr 604:117-23
Bucci, E; Fronticelli, C; Razynska, A et al. (1992) Hemoglobin tetramers stabilized with polyaspirins. Biomater Artif Cells Immobilization Biotechnol 20:243-52
Gryczynski, Z; Tenenholz, T; Bucci, E (1992) Rates of energy transfer between tryptophans and hemes in hemoglobin, assuming that the heme is a planar oscillator. Biophys J 63:648-53
Urbaitis, B K; Razynska, A; Corteza, Q et al. (1991) Intravascular retention and renal handling of purified natural and intramolecularly cross-linked hemoglobins. J Lab Clin Med 117:115-21
Razynska, A; Fronticelli, C; Di Cera, E et al. (1990) Effect of temperature on oxygen affinity and anion binding of bovine hemoglobin. Biophys Chem 38:111-5
Bucci, E; Steiner, R F (1990) Perturbation of molecular species distribution in steady states supported by a flow of energy. Models analogous to Ca2(+)-dependent ATPase and phosphorylase b. Biophys Chem 37:61-71

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