Hemoglobins with intersubunit desulfide bonds

Details Hemoglobins with intersubunit desulfide bonds Hemoglobins with intersubunit desulfide bonds

1993-11-29

1995-09-12

Walsh, Stephen G.

Chemistry: natural resins or derivatives; peptides or proteins;

Proteins, i.e., more than 100 amino acid residues

Blood proteins or globulins, e.g., proteoglycans, platelet...

C07K 14805, A61K 3842

Patent

active

054497590

ABSTRACT:
Cysteine substitution mutants of alpha and/or beta globin mutants are produced by recombinant DNA techniques and used in the construction, intracellularly or otherwise, of mutant hemoglobins in which alpha- and beta-globin like subunits are crosslinked by disulfide bonds. Solutions of these mutant hemoglobins are used as blood substitutes.
Preferably, these mutant hemoglobins contain further mutations which reduce their affinity for oxygen.
Hemoglobins are preferably obtained by recombinant DNA techniques. Both alpha and beta globin chains can now be readily expressed, making possible the commercial production of wholly artificial hemoglobin, whether conventional or mutant in form. Solutions of wholly artificial hemoglobins are also used as blood substitutes. Expression of the alpha globin gene was substantially improved by means of a beta globin gene "header".

REFERENCES:
patent: 4001200 (1977-01-01), Bonsen et al.
patent: 4001401 (1977-01-01), Bonsen et al.
patent: 4053590 (1977-10-01), Bonsen et al.
patent: 4061736 (1977-12-01), Morris et al.
patent: 4336248 (1982-06-01), Bonhard et al.
patent: 4473496 (1984-09-01), Scannon
patent: 4529719 (1985-07-01), Tye
patent: 4584130 (1986-04-01), Bucci et al.
patent: 4598064 (1986-07-01), Walder
patent: 4600531 (1986-07-01), Walder
patent: 4670417 (1987-06-01), Iwasaki et al.
patent: 4730936 (1988-03-01), Thorjusen, Jr.
patent: 4738952 (1988-04-01), Ecanow et al.
patent: 4777244 (1988-10-01), Bonhard et al.
patent: 4839419 (1989-06-01), Kraemer et al.
patent: 4920194 (1990-04-01), Feller et al.
patent: 5028588 (1991-07-01), Hoffman et al.
patent: 5239061 (1993-08-01), Fronticelli et al.
Bunn et al. in "Hemoglobin: Molecular, Genetic, and Clinical Aspects" W.B. Saunders Co, Philadelphia, (1986) pp. 13-35 & 381-451.
White et al. (1978) "Principles of Biochemistry", 6th ed., McGraw-Hill, N.Y., pp. 950-959.
Metzler (1977) "Biochemistry-The Chemical Reactions of Living Cells", Academic Press, N.Y., pp. 226-237.
Honig et al., "Hemoglobin Nigeria (.alpha.-81 Ser->Cys): A New Variant Associated with .alpha.-Thalassemia", Blood, vol. 55, No. 1, pp. 131-137, Jan. 1980.
Tondo et al., "Functional Properties of Hemoglobin Porto Alegre (.alpha..sub.2.sup.A B.sub.2.sup.9 Ser-> Cys) and the Reactivity of its Extra Cysteinyl Residue", Biochimica et Biophysica Acta, 342: pp. 15-20, 1974.
Adams et al., "HB Mississippi [44(CD3)Ser-Cys]: A New Variant With Anomalous Properties", Hemoglobin, 11(5), 435-452, 1987.
Blackwell et al., "Hemoglobin Ta-Li: .beta.83 Gly->Cys", Biochimica et Biophysica Acta, 243: pp. 467-474, 1971.
Herskovits et al., "The Homoglobin of the Aquatic Snail", Planorbella Duryi (Wetherby), Comp. Biochem. Physiol., vol. 95B, No. 2, pp. 321-326, 1990.
Suzuki et al., "Primary structure of a constituent polypeptide chain (AIII) of the giant Haemoglobin from the deepsea tube worm Lamellibrachia", Biochem. J., 266: pp. 221-225, 1990.
Fushitani et al., "The Amino Acid Sequences of Chains a, b, and c That Form the Trimer Subunit of the Extracellular Hemoglobin from Lumbricus terrestris", The Journal of Biological Chemistry, vol. 263, No. 14, pp. 6502-6517, 1988.
Fushitani et al., "The Extracellular Hemoglobin of the Earthworm, Lumbricus terrestris", The Journal of Biological Chemistry, vol. 266, No. 16, pp. 10275-10281, Jun. 1991.
Riggs, Austin, "Hemoglobin Polymerization in Mice", Science, pp. 621-623, Feb. 1965.
Bonaventura, Joseph, "Polymerization of Hemoglobins of Mouse and Man: Structural Basis", Science, pp. 800-802, Nov. 1967.
Peters et al., "A mouse .beta.-globin mutant that is an exact model of hemoglobin rainier in man", Genetics, 110: pp. 709-721, Aug. 1985.
Ishimoto et al., "A Variant Hemoglobin Found in Macaca fuscata: Anther Polymerizing Hemoglobin of Macaques", J. Anthro. Soc. Nippos., 83(3): 233-243, 1975.
Takenaka et al., "Hemoglobin Izu(Macaca): .beta.83 (EF 7) Gly->Cys. A New Hemoglobin Variant Found in the Japanese Monkey (Macaca Fuscata)", Biochimica et Biophysica Acta, 492: pp. 433-444, 1977.
Tam et al., "The Hemoglobins of the Bullfrog Rana catebeiana", The Journal of Bilogical Chemistry, vol. 261, No. 18, pp. 8290-8294, 1986.
Riggs et al., "Polymerization of Frog and Turtle Hemoglobins", Biochemistry: Riggs, Sullivan, and Agee, Proc. N.A.C., vol. 51, pp. 1127-1134, 1964.
Keipert et al., "Pyridoxylated-Polyhemoglobin Solution: A Low Viscosity Oxygen-Delivering Blood Replacement Fluid with Normal Oncotic Pressure and Long-Term Storage Feasibility", Biomat., Art. Cells, Art. Org., 16(1-3), 185-196, 1988.
Benesch et al., "Enhanced oxygen unloading by an interdimerically crosslinked hemoglobin in an isolated perfused rabbit heart", Proc. Natl. Acad. Sci. USA, vol. 81, pp. 2941-2943, May 1984.
Benesch et al., "Bis-Pyridoxal Polyphosphates: A New Class of Specific Intramolecular Crosslinking Agents for Hemoglobin", Biochemical and biophysical Research Communications, vol. 156, No. 1, pp. 9-14, 1988.
Yabuki et al., "Characterization of pyridoxalated hemoglobin-polyxyethylene conjugate as a physiologic oxygen carrier", Transfusion, vol. 30, No. 6, pp. 516-520, 1990.
van der Plas et al., "Purification and physical characteristics of a hemoglobin solution modified by coupling to 2-nor-2-formylpyridoxal 5'-phosphate (NFPLP)", Transfusion, vol. 28, No. 6 pp. 525-530, 1988.
White et al., "Effects of CrossLinking on the Thermal Stability of Hemoglobin", Archives of Biochemistry and Biophysics, vol. 258, No. 1 pp. 51-57, Oct. 1987.
Yang et al., "The Effect of CrossLinking by BIS(3,5,-Dibromosalicyl) Fumarate on the Autoxidation of Hemoglobin", Biochemical and Biophysical Research Communication, vol. 163, No. 2, pp. 733-738, 1989.
Bellelli et al., "Cooperative Ligand Binding of CrossLinked Hemoglobins at Very High Temperatures", J. Mol. Biol., 213: pp. 571-574, 1990.
Yang et al., "Thermal Stability of Hemoglobin CrossLinked in the T-State by BIS(3,5-Dibromosalicyl) Fumarate", Biochemical and Biophysical Research Communications, vol. 174, No. 2, pp. 518-523, 1991.
Scannon, Patrick J., "Molecular modifications of hemoglobin", Critical Care Medicine, vol. 10, No. 4, pp. 261-265, Apr. 1982.
Manning et al., "Preparation, properties, and plasma retention of human hemoglobin derivatives: Comparison of uncrossLinked carboxymethylated hemoglobin with crossLinked tetrameric hemoglobin", Proc. Natl. Acad. USA vol. 88 pp. 3329-3333, Apr. 1991.
Suganuma et al., "Elimination of Disulfide Bonds Affects Assembly and Secretion of the Human Chorionic Gonadotropin .beta. Subunit", The Journal of Biological Chemistry, vol. 264, No. 32 pp. 19302-19307, 1989.
Sauer et al., "An Engineered Intersubunit Disulfide Enhances the Stability and DNA Binding of the N-Terminal Domain of Repressor", Biochemistry, 25: pp. 5992-5998, 1986.
Gitelson et al, "Two-stage thermal unfolding of [Cys.sup.55 ]-substituted Cro repressor of bacteriophage", FEBS, voo. 289, No. 2, pp. 201-204, Sep. 1991.
Ranty et al., "An intra-dimeric crossLink of Large subunits of spinach ribulose-1,5-biphosphate carboxylase/oxygenase is formed by oxidation of cysteine 247", FEBS, pp. 353-358, 1991.
Matsumura et al., "Stabilization of phage T4 Lysozyme by engineered disulfide bonds", Proc. Natl. Acad. Sci. vol. 86, pp. 6562-6566, Sep. 1989.
Matsumura et al., "Control of Enzyme Activity by an Engineered Disulfide Bond", Science, vol. 243, pp. 792-794, Feb. 1989.
Perry et al., "Disulfide Bond Engineered into T4 Lysozyme: Stabilization of the Protein Toward Thermal Inactivation", Science, vol. 226, pp. 555-557 Nov. 1984.
Matsumura et al., "Substantial increase of protein stability by multiple disulphide bonds", Nature, vol. 342, pp. 291-293, Nov. 1989.
Villafranca et al., "An Engineered Disulfide Bond in Dihydrofolate Reductase", Biochemistry, vol. 26: pp. 2182-2189, 1987.
Pantoliano et al., "Protein Engineering of Subtilisin BPN': Enhanced Stabilization through the Introduction of Two Cysteines to Form a Disulfide Bond", Biochemistry, 26: pp. 2077-2082, 1987.
Wells et al., "In Vivo Formation and Stability of Engineered Disulfide Bonds in Subtilisin", The Journal of Biological Chemistry, vo

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