Abstract: Water-soluble prodrugs of the formula: ##STR1## wherein: D is a biologically active nucleophile;M is X or Q;x is an electron withdrawing group;Q is a moiety containing a free electron pair positioned five or six atoms from Y';Y and Y' are oxygen or sulfur;R is a polyalkylene oxide; andZ is OH, C.sub.1-4 alkyl moieties or ##STR2## are disclosed.

Abstract: Poly(ethylene glycol)-N-succinimide carbonate and its preparation are disclosed. Polyethylene glycol (PEG) is converted into its N-succinimide carbonate derivative. This form of the polymer reacts readily with amino groups of proteins in aqueous buffers. The modified proteins have PEG-chains grafted onto the polypeptide backbone by means of stable, hydrolysis-resistant urethane (carbamate) linkages.

Abstract: The present invention is directed to methods of preparing high purity polyalkylene oxide carboxylic acids. The methods include reacting a polyalkylene oxide such as polyethylene glycol with a t-butyl haloacetate in the presence of a base followed by treatment with an acid such as trifluoroacetic acid. The resultant polymer carboxylic acids are of sufficient purity so that expensive and time consuming purification steps required for pharmaceutical grade polymers are avoided.

Abstract: Water-soluble azlactone activated polyalkylene oxides having improved hydrolytic stability and conjugates of the azlactone activated polyalkylene oxides with biologically active nucleophiles are disclosed. Methods of forming and conjugating the activated polyalkylene oxides with biologically active nucleophiles are also disclosed.

Abstract: Disclosed are 7-substituted taxoid derivatives, in particular taxol-7-carbazates which have improved water-solubility and/or enhanced therapeutic activity and methods of making the same. The preferred taxoid derivatives have the formula: ##STR1## wherein Z is H or ##STR2## Y=O or S; X=CH.sub.2 or O; n=zero or a positive integer, preferably one; with the proviso that when n=O, X=CH.sub.2 ; R=C.sub.1 -C.sub.4 alkyl, haloalkyl, carboxyalkyl, thioalkyl, sulfonylalkyl, phenyl, hydroxyphenyl, aminophenyl, carboxyphenyl, a polyalkyleneoxide homopolymer or water soluble polyalkyleneoxide containing copolymer, having a molecular weight of from about 1,000 to about 20,000; ##STR3## W=O, N--L, S or SO.sub.2 ; Ph is a phenyl group; L=H, C.sub.1 -C.sub.4 alkyl or phenyl; and R.sub.2 =C.sub.1-C.sub.4 alkyl, phenyl or a polyalkyleneoxide homopolymer or water soluble polyalkyleneoxide containing copolymer, having a molecular weight of from about 1,000 to about 20,000.

Abstract: Methods of treating mammalian neoplastic disease are disclosed using phospholipase A.sub.2 activating proteins and fragments thereof.

Abstract: The use of hemoglobin-polymer conjugates to enhance antitumor therapy in mammals is disclosed. The methods include administering an effective amount of an antitumor therapy such as radiation in combination with hemoglobin conjugated to a substantially non-antigenic polymer.

Abstract: Hemoglobin-containing solutions containing polyalkyene oxide-conjugated hemoglobin having a molecular weight greater than about 85,000 daltons and a degree of substitution of at least five polyalkylene oxide conjugates per hemoglobin molecule are described that are not associated with hemoglobinuria in mammals. A method of simultaneously fractionating and purifying polyalkylene oxide-conjugated hemoglobins is also disclosed.

Abstract: Copolymers of poly(alkylene oxides) and amino acids or peptide sequences are disclosed, which amino acids or peptide sequences have pendant functional groups that are capable of being conjugated with pharmaceutically active compounds for drug delivery systems and cross-linked to form polymer matrices functional as hydrogel membranes. The copolymers can also be formed into conductive materials. Methods are also disclosed for preparing the polymers and forming the drug conjugates, hydrogel membranes and conductive materials.

Abstract: Water-soluble cyclic imide thione activated polyalkylene oxides having improved hydrolytic stability are disclosed. Methods of forming and conjugating the activated polyalkylene oxides with biologically active nucleophiles are also disclosed.

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.

Abstract: Water-soluble cyclic imide thione activated polyalkylene oxides having improved hydrolytic stability are disclosed. Methods of forming and conjugating the activated polyalkylene oxides with biologically active nucleophiles are also disclosed.

Abstract: Poly(ethylene glycol)-N-succinimide carbonate and its preparation are disclosed. Polyethylene glycol (PEG) is converted into its N-succinimide carbonate derivative. This form of the polymer reacts readily with amino groups of proteins in aqueous buffers. The modified proteins have PEG-chains grafted onto the polypeptide backbone by means of stable, hydrolysis-resistant urethane (carbamate) linkages.

Abstract: Water-soluble azlactone activated polyalkylene oxides having improved hydrolytic stability and conjugates of the azlactone activated polyalkylene oxides with biologically active nucleophiles are disclosed. Methods of forming and conjugating the activated polyalkylene oxides with biologically active nucleophiles are also disclosed.

Abstract: Hemoglobin-containing solutions containing polyalkylene oxide-conjugated hemoglobin having a molecular weight greater than about 85,000 daltons and a degree of substitution of at least five polyalkylene oxide conjugates per hemoglobin molecule are described that are not associated with hemoglobinuria in mammals. A method of simultaneously fractionating and purifying polyalkylene oxide-conjugated hemoglobins is also disclosed.

Abstract: Water-soluble aryl imidate activated polyalkylene oxides having improved hydrolytic stability and conjugates of the aryl imidate activated polyalkylene oxides with biologically active nucleophiles are disclosed. Methods of preparing the activated polyalkylene oxides and conjugates thereof are also disclosed.

Abstract: Methods are disclosed for separating hemoglobin from erythrocytes by contacting erythrocytes with a hypotonic buffer solution at a rate sufficient to render the release of hemoglobin from said erythrocytes without significant lysis. The hemoglobin is then separated from the erythrocytes. Methods are also disclosed for purifying hemoglobin solutions of DNA, endotoxins and phospholipids by contacting the hemoglobin solutions with an anion exchange medium.

Abstract: The invention pertains to a single polypeptide chain binding molecule which has binding specificity and affinity substantially similar to the binding specificity and affinity of the light and heavy chain aggregate variable region of an antibody, to genetic sequences coding therefor, and to recombinant DNA methods of producing such molecule and uses for such molecule.

Abstract: The invention relates to subtilisin enzymes which have been modified by mutating a nucleotide sequence (gene) coding for the subtilisin. The modified subtilisin enzymes have enhanced thermal stability.

Abstract: Recombinant production of bioadhesive precursor protein analogs is disclosed. The bioadhesive precursor protein analogs can be hydroxylated and used as an adhesive in wet environments.