Abstract: The present invention is directed at variant proteins and polypeptides having an enhanced affinity, i.e., greater binding strength, for immobilized-metal affinity resins and resides in engineering one or more specific metal-chelating amino acid sequences into a protein or polypeptide, the specific sequence depending on the metal-binding amino acids utilized and the secondary structure associated with the portion of the protein or polypeptide to include such sequence.

Abstract: A method and apparatus for the continuous separation of a target protein from a protein mixture containing two or more proteins and at a pH equal to the pI of the target protein is disclosed. The method and apparatus employ a non-ionic, non-electrically conductive porous conduit through which the protein mixture is passed. The conduit is subjected to the influence of an electrical field substantially perpendicular to the flow of fluid therethrough resulting in movement of all charged protein from the conduit lumen. The target protein, which is unaffected by the electric field since it is not charged at a pH equal to its pI, is collected from the conduit outlet in substantially purified form.

Abstract: The disclosure describes novel immunosuppressive agents isolated from syncytiotrophoblast microvilli membranes by preparing a minutely subdivided and solubilized preparation of said membranes and isolating the unreduced N-linked oligosaccharides from an extract of the preparation.

Abstract: Novel blood coagulation inhibitors are disclosed which are peptide fragments comprising (A) Kunitz-type domain two of lipoprotein-associated coagulation inhibitor which inhibits Factor Xa production and (B) Kunitz-type domains one and two of lipoprotein-associated coagulation inhibitor which inhibits Factor VIIa/TF enzymatic complex formation.

Abstract: A modified heparin cofactor II is disclosed, HCII (Leu.sub.444 .fwdarw.Arg), which has substantially improved inhibitory activity against thrombin compared to native HCII or antithrombin.

Abstract: A method is provided for converting therapeutic glycosidase inhibitors to novel prodrugs by phosphorylation of a free hydroxyl group on the molecule to substantially reduce the glycosidase inhibitory activity without thereby substantially reducing the therapeutic activity.

Abstract: A method of oligosaccharide sequencing in which the components are determined essentially simultaneously is disclosed which comprises a series of steps as follows:A. Placing an identifying label on the reducing terminal residue of the oligosaccharide to be sequenced,B. Dividing said oligosaccharide into a plurality of separate portions of known integer amounts,C. Treating each said portion with a different reagent mix to thereby provide a series of reaction mixtures,D. Pooling known integer amounts of the products from each separate reaction mixture to give a product pool,E. Performing an analysis on said product pool which measures the molar proportions of the reaction products, andF. Reconstructing or identifying the starting oligosaccharide from the molar prevalence of said reaction products.

Abstract: A modified t-PA having improved in vivo half-life is disclosed comprising in sequence a sequence of two K2 kringle regions and a serine protease region SP.

Abstract: .alpha.-Homojirimycin and 6-dpi-homojirimycin are each synthesized from 2 az ido-2-deoxy-3,4:6,7-di-O-isopropylidene-D-glycero-D-talo-heptono-1,5-la ctone in which the side chain acetonide is hydrolyzed to give the corresponding diol which is then protected with a silyl protecting agent to form a silyl ether. The latter compound is used as a divergent intermediate in which the piperidine ring is formed by joining the nitrogen function at C-2 to C-6 (A) with inversion of configuration at C-6 to form 6-epi-homomannojirimycin or (B) with retension of configuration at C-6 to form .alpha.-homomannojirimycin.

Abstract: The synthesis of the novel fucosidase inhibitors, .beta.-L-homofuconojirimycin and related 1-.beta.-C-substituted deoxymannojirimycins, is disclosed.

Abstract: The synthesis of the novel fucosidase inhibitor, 2,6-imino-2,6,7-trideoxy-D-glycero-D-gluco heptitol, is disclosed.

Abstract: Microbial cells are immobilized by entrapment in gellan gum, also known as deacetylated heteropolysaccharide S-60. Entrapment can be carried out by forming a mixture of a paste of microbial cells and an aqueous solution of gellan gum and adding the mixture drop-wise to an aqueous solution of cations to produce beads of hardened gellan gum entrapping the microbial cells. The microbial cells preferably contain aspartase activity and can be E. coli ATCC 11303, and the cations are preferably magnesium ions. In an alternative embodiment, the mixture of microbial cell paste and aqueous gellan gum solution is admixed with a porous cationic exchange resin which is preferably in magnesium ion form and the microbial cells are entrapped in hardened gellan gum in and on the resin.

Abstract: Novel peptide mimetic compounds are provided which have useful activity as inhibitors of platelet aggregation. These compounds have the chemical structure ##STR1## wherein x=4 to 8,y=0 to 4,W=CH.sub.2 --CH.sub.2 or C.dbd.CH,Z=H, COOH, CONH.sub.2, CH.sub.2 OH, CO.sub.2 R, CH.sub.2 OR or C.sub.1-6 alkyl,R=C.sub.1-6 alkyl,Ar=a nitrogen-containing heterocyclic group, andAsp=aspartic acid residue.

Abstract: Biological materials such as enzymes, proteins and peptides are encapsulated by forming a mixture of the material and an aqueous non-ionic polymer solution, spraying the mixture into a circulating water-immiscible nonsolvent for the polymer at a temperature sufficient to freeze the beads and drying the frozen beads to remove essentially all unbound water such as to provide a water content of about 1-2 weight percent. Suitable non-ionic polymers are poly(vinyl alcohol), polyvinylpyrollidone, dextran and derivatized cellulose. A densification agent such as alumina may be present in the polymer solution to enhance specific gravity of the beads formed. Encapsulated material such as microbes produced by this process provide useful agricultural agents which can be delivered to the market in a dormant state and suitable for delivery to soil or plant leaves. The beads can be applied dry, via a planting or an insecticide box, or wet via a spray nozzle.

Abstract: A group of five- and six-membered heterocyclic compounds having a nitrogen in the ring and 2 to 3 hydroxyl substituents on the ring are effective inhibitory agents of human immunodeficiency virus.

Abstract: A method of increasing the specific activity of tissue plasminogen activator is disclosed which comprises increasing the proportion of neutral oligosaccharides in the tissue plasminogen activator glycoprotein.

Abstract: Disclosed herein are compounds of the class of peptides having from about 4 to about 8 amino acid residues that are substrates for retroviral protease, e.g., HIV protease, derived from known cleavage sites and that are modified to contain an internal COCH.sub.2 bond isostere, useful as inhibitors of said retroviral protease, e.g., HIV protease, and exemplified by the modified peptide, Abz-Thr-Ile-Nle.PSI.(K)Nle-Gln-Arg-NH.sub.2, wherein K is COCH.sub.2.

Abstract: Novel diheteroatom-substituted fatty acid analog substrates of myristoylating enzymes are provided which contain oxyen and/or sulfur in place of two methylene groups in carbon positions from 3 to 13 in the fatty acid chain of a C.sub.13 -C.sub.14 fatty acid analog or alkyl ester thereof in which said oxygen or sulfur atoms are separated by at least one methylene group.

Abstract: Swainsonine and analogs, namely 1,4-dideoxy-1,4-imino-D-mannitol and the novel ring contracted swainsonines, .DELTA.(1S,2R,7R,7aR)-1,2-trihydroxypyrrolizidine and (1S,2R,7S,7aR)-1,2,7-trihydroxypyrrolizidine, are synthesized from the divergent intermediate, 4,5-anhydro-1-azido-1-deoxy-2,3-O-isopropylidene-D-talitol. These novel compounds are glycosidase inhibitors.

Abstract: Swainsonine and analogs, namely, 1,4-dideoxy-1,4-imino-D-mannitol and the novel ring contracted swainsonines, (1S,2R,7R,7aR)-1,2-trihydroxypyrrolizidine and (1S,2R,7S,7aR)-1,2,7-trihydroxypyrrolizidine, are synthesized from the divergent intermediate, 4,5-anhydro-1-azido-1-deoxy-2,3-O-isopropylidene-D-talitol. These novel compounds are glycosidase inhibitors.