Derivatives of human haemoglobin, method for preparing them, pro

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...

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530399, C07K 14805, A61K 3842

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active

055147801

ABSTRACT:
The invention relates, as new compounds, to derivatives of tetrameric human haemoglobin corresponding to the covalent coupling of a haemoglobin tetramer and a polycarboxy-substituted compound having at least 4 -COO.sup.- groups, the said polycarboxy-substituted compound effecting an internal crosslinking of the two dimers of haemoglobin and conferring thereon an affinity for oxygen which is compatible with an in vivo use of the conjugate when the natural allosteric effector of haemoglobin is not present. Among carboxy-substituted compounds, special mention is made of benzenehexacarboxylate and benzenetetracarboxylate.

REFERENCES:
patent: 5079337 (1992-01-01), Leonard et al.
patent: 5110909 (1992-05-01), Dellacherie et al.
patent: 5349054 (1994-09-01), Bonaventura et al.
Banerjee, R. and Allan Desbois, "Effet des avions polycarboxylate sur l'benioqohine" C. R. Acad Sci. Paris, t. 277 (17 Sep. 1973).
Desbois, A. and R. Banerjee "Effects of Polyvalent Anion Binding to Hemoglobin on Oxygen and Oxidation-Reduction Equilibria and their Relevance to Allosteric Transition" J. Mol. Biol., (1975) 92, 479-493.
Dellacherie, E. and M. Leonard, "Improvement of Oxygen-Carrying Properties of Human Hemoglobin by Chemical Modification with a Benzene Hexacarboxylate-Monosubstituted Polyoxyethylene", Journal of Protein Protein Chemistry, vol. 10, No. 1, 1991, 61-67.
Labrude, P., B. Teisseire and C. Vigneron, "Attempts to use carbodiimide (EDCI) to cross-link hemoglobin for transfusions", Faculte des Sciences Pharmaceutiques et Biologiques, 26 Jul. 1978.
Estep, T. N.; E. W. Bobka; A. A. Ebeling; T. T. Hai; D. J. Nelson; R. J. Pankau, and A. Srnak, "Novel Aspects of Diaspirin Cross-Linked Hemoglobin Synthesis and Purification", International Symposium on Red Cell Red Cell Substitutes: Design and Clinical Applications, San Francisco, CA May 16-19, 1989, p. 21.
Bucci, E.; C. Fronticelli; A. Razynska; and B. Urbaitis, "Overview of Chemically Obtained Oxygen Carriers From Hemoglobin: Pseudocrosslinked Tetramers", International Symposium on Red Cell Substitutes: Design and Clinical Applications, San Francisco, CA, May 16-19, 1989, p. 22.

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