Abstract: The invention relates to novel recombinant hemoglobins having reduced nitric oxide scavenging and/or increased high soluble expression. The invention further relates to methods of increasing the soluble expression of recombinant hemoglobin by adding exogenous hemin in molar excess of the heme binding sites of recombinant hemoglobin.

Abstract: The invention relates to novel recombinant hemoglobins having reduced nitric oxide scavenging and/or increased high soluble expression. The invention further relates to methods of increasing the soluble expression of recombinant hemoglobin by adding exogenous hemin in molar excess of the heme binding sites of recombinant hemoglobin.

Abstract: The invention relates to novel recombinant hemoglobins having reduced nitric oxide scavenging and/or increased high soluble expression. The invention further relates to methods of increasing the soluble expression of recombinant hemoglobin by adding exogenous hemin in molar excess of the heme binding sites of recombinant hemoglobin.

Abstract: The present invention relates to globins containing non-naturally occurring binding domains, In particular, the present invention is directed toward a binding domain comprising the oligomerizing domain GCN4 and GCN4 derivatives. Thc present invention also relates to multimeric hemoglobins comprised of at least one globin containing at least one non-naturally occurring binding domain.

Abstract: This invention relates to recombinant hemoglobins containing mutations in or near the heme pocket of the hemoglobin molecule. This invention particularly relates to recombinant hemoglobins that have altered geometry or polarity around the distal portion of the heme pocket.

Abstract: DNA molecules which encode pseudodimeric globin-like polypeptides with an asymmetric cysteine mutation suitable for crosslinking two tetramers, or which encode pseudooligomeric globin-like polypeptides comprising four or more globin-like domains, are useful in the preparation of multimeric hemoglobin-like proteins.

Abstract: The present invention relates to methods of controlling beta dimer formation in hemoglobin solutions by altering the metal binding site adjacent to the N-terminus of beta globins. The invention further relates to methods of producing stable, intramolecularly crosslinked beta globins by exposure to Ni(II) and oxone.

Abstract: The present invention relates to cross-linked hemoglobins, and particularly to methods of controlling the functionality of such hemoglobins. The controlled functionalities include the P.sub.50 and the Hill coefficient. The present invention provides methods for producing a cross-linked hemoglobin with specific final functionalities by regulating the amount of both total hemoglobin and R-state hemoglobin prior to cross-linking, and by modulating cross-linking reaction conditions such as time, temperature, pH and the ratio of cross-linking reagent to hemoglobin.

Abstract: The present invention relates to modified hemoglobin-like polypeptides containing multiple dialpha (or dibeta) domains. The present invention also relates to multimeric hemoglobin-like proteins comprising covalently joined hemoglobin-like moieties. Another aspect of the inention is directed at a purification method of hemoglobin-like polypeptides utilizing ion exchange chromatography.

Abstract: The present invention relates to recombinant hemoglobin solutions containing reduced amounts of protoporphyrin IX and to methods of producing such hemoglobin solutions. The methods are accomplished by overexpressing the hemH gene in a suitable host cell or by increasing the production of hemH in a host cell, for example, by integration of the hemH gene into the chromosome of the host cell or by inserting multiple copies of the gene in host cells naturally having a hemH gene.

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 glolbin gene was substantially improved by means of a beta globin gene "header".

Abstract: Disclosed is a mutant human .beta. globin modified so as to exhibit, when present as part of a hemoglobin molecule, an altered bicarbonate effect compared to the unmodified .beta. globin. The .beta. globin is modified to contain at positions 29-41 at least two non-wild type amino acid residues selected from the group consisting of amino acid residues 29-41 of crocodile .beta.-globin SEQ ID NO:2 to produce an enhanced bicarbonate effect.

Abstract: The present invention relates to storage stable hemoglobin solutions which contain partially deoxygenated and surprisingly low amounts of reducing agents. Methods for preparing such storage stable hemoglobin solutions are also provided as well as a systems for storing the solutions.

Abstract: The present invention relates to hemoglobin compositions stabilized against the formation of aggregates. Such compositions contain at least a surfactant, said surfactant not being an adduct of a polymer and an anionic ligand. The present invention further relates to methods of making such hemoglobin compositions.

Abstract: The present invention relates to methods of purifying proteins having surface active, electron-rich amino acids using an aqueous two phase system. The methods include the use of salts and inert hydrophobic molecules, such as polymers, to produce the aqueous two phase system and the use a polymer-chelator-metal complex to purify the target proteins.