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...
Patent
1992-05-22
1995-01-31
Cashion, Jr., Merrell C.
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...
530815, C07K 1300, C07K 1708
Patent
active
053860144
ABSTRACT:
The present invention relates to chemically modified hemoglobin produced by a novel and efficient method in which stroma-free hemoglobin is first effectively deoxygenated and reduced and then conjugated with a polyalkylene oxide such as polyethylene glycol (PEG) under conditions which maintain the structural integrity of the heme oxygen binding site. In specific, preferred embodiments of the invention, the deoxygenation and reduction is performed under an inert atmosphere by the amino acid cysteine. In additional specific, preferred embodiments, the structural integrity of the heme oxygen binding site is maintained by a high anionic concentration in the reaction mixture. In further preferred specific emodiments of the invention, the polyalkylene oxide is polyethylene glycol; in still further preferred specific embodiments of the invention, the polyalkylene oxide is linked to hemoglobin via a urethane (carbamate) linkage.
The novel PEG-modified hemoglobin compounds of the invention exhibit superior oxygen transport capabilities, extended half-life, and importantly, low immunogenicity.
REFERENCES:
patent: 4179337 (1979-12-01), Davis et al.
patent: 4377512 (1983-03-01), Ajisaka et al.
patent: 4412989 (1983-11-01), Iwashita et al.
patent: 4529719 (1985-07-01), Tye et al.
patent: 4584130 (1986-04-01), Bucci et al.
patent: 4698387 (1987-10-01), Schmidt et al.
patent: 4857636 (1989-08-01), Hsia
patent: 4900780 (1990-02-01), Cerny et al.
patent: 4902502 (1990-02-01), Nitecki et al.
patent: 5006333 (1991-04-01), Saifer et al.
Bunn, Science, 172, 1049-50 (1971).
Breepoel et al., Pflugers. Arch., 389, 219-20 (1981).
Fronticelli et al., J. Biol. Chem., 259(17), 10841-44 (Sep. 10, 1984).
Bucci et al., Biomat., Art. Cells, Art. Org., 16(1-3), 197-207 (1988).
Yabuki et al., Transfusion, 30, 516-20 (1990).
Agishi et al., Biomat. Art. Cells, Art. Org., 16, 261-70 (1988).
Labrude et al., Int. J. Artif. Organs, 11, 393-402 (1988).
Leonard et al., Makromol. Chem., 189, 1809-17 (1988).
Matsushita et al., Biomat. Art. Cells, Art. Org., 16, 247-60 (1988).
Nishi et al., Biomat., Art. Cells, Art. Org., 16, 653-5 (1988).
Iwashita et al., Biomat., Art. Cells, Art. Org., 16, 271-80 (1988).
Matsushita et al., Trans. Am. Soc. Artif. Intern. Organs, 33, 352-5 (1987).
Zygmunt et al., Int. J. Biol. Macromol., 9, 343-5 (1987).
Iwasaki et al., Artf. Organs, 10, 470-4 (1986).
Iwasaki et al., Artf. Organs, 10, 411-6 (1986).
Matsushita et al., Trans. Am. Soc. Artif. Intern. Organs, 32, 490-4 (1986).
Leonard et al., Biochem. Biophys. Acta, 791, 219-25 (1984).
Leonard et al., Tetrahedron, 40, 1581-4 (1984).
Davis Frank
Nho Kwang
Zalipsky Shmuel
Cashion Jr. Merrell C.
Enzon Inc.
Mercanti Michael N.
Salata Carol A.
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