- Rational engineering ofAcinetobacter tandoiiglutamate dehydrogenase for asymmetric synthesis ofl-homoalanine through biocatalytic cascades
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l-Homoalanine, a useful building block for the synthesis of several chiral drugs, is generally synthesized through biocascades using natural amino acids as cheap starting reactants. However, the addition of expensive external cofactors and the low efficiency of leucine dehydrogenases towards the intermediate 2-ketobutyric acid are two major challenges in industrial applications. Herein, a dual cofactor-dependent glutamate dehydrogenase fromAcinetobacter tandoii(AtGluDH) was identified to help make full use of the intracellular pool of cofactors when using whole-cell catalysis. Through reconstruction of the hydrophobic network between the enzyme and the terminal methyl group of the substrate 2-ketobutyric acid, the strict substrate specificity ofAtGluDH towards α-ketoglutarate was successfully changed, and the activity obtained by the most effective mutant (K76L/T180C) was 17.2 times higher than that of the wild-type protein. A three-enzyme co-expression system was successfully constructed in order to help release the mass transfer restriction. Using 1 Ml-threonine, which is close to the solubility limit, we obtained a 99.9% yield ofl-homoalanine in only 3.5 h without adding external coenzymes to the cascade, giving 99.9% ee and a 29.2 g L?1h?1space-time yield. Additionally, the activities of the engineeredAtGluDH towards some other hydrophobic amino acids were also improved to 1.1-11.2 fold. Therefore, the engineering design of some dual cofactor-dependent GluDHs could not only eliminate the low catalytic activity of unnatural substrates but also enhance the cofactor utilization efficiency of these enzymes in industrial applications.
- Diao, Shiqing,Jiang, Shuiqin,Liu, Yan,Sun, Yangyang,Wang, Hualei,Wang, Liuzhu,Wei, Dongzhi
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p. 4208 - 4215
(2021/06/30)
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- Mechanistic insight into metal ion-catalyzed transamination
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Several classes of biological reactions that are mediated by an enzyme and a co-factor can occur, to a slower extent, not only without the enzyme but even without the co-factor, under catalysis by metal ions. This observation has led to the proposal that metabolic pathways progressively evolved from using inorganic catalysts to using organocatalysts of increasing complexity. Transamination, the biological process by which ammonia is transferred between amino acids and α-keto acids, has a mechanism that has been well studied under enzyme/co-factor catalysis and under co-factor catalysis, but the metal ion-catalyzed variant was generally studied mostly at high temperatures (70-100 °C), and the details of its mechanism remained unclear. Here, we investigate which metal ions catalyze transamination under conditions relevant to biology (pH 7, 20-50 °C) and study the mechanism in detail. Cu2+, Ni2+, Co2+, and V5+ were identified as the most active metal ions under these constraints. Kinetic, stereochemical, and computational studies illuminate the mechanism of the reaction. Cu2+ and Co2+ are found to predominantly speed up the reaction by stabilizing a key imine intermediate. V5+ is found to accelerate the reaction by increasing the acidity of the bound imine. Ni2+ is found to do both to a limited extent. These results show that direct metal ion-catalyzed amino group transfer is highly favored even in the absence of co-factors or protein catalysts under biologically compatible reaction conditions.
- Mayer, Robert J.,Kaur, Harpreet,Rauscher, Sophia A.,Moran, Joseph
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supporting information
p. 19099 - 19111
(2021/11/22)
-
- Electrosynthesis of amino acids from biomass-derivable acids on titanium dioxide
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Seven amino acids were electrochemically synthesized from biomass-derivable α-keto acids and NH2OH with faradaic efficiencies (FEs) of 77-99% using an earth-Abundant TiO2 catalyst. Furthermore, we newly constructed a flow-Type electrochemical reactor, named a "polymer electrolyte amino acid electrosynthesis cell", and achieved continuous production of alanine with an FE of 77%.
- Fukushima, Takashi,Yamauchi, Miho
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supporting information
p. 14721 - 14724
(2019/12/24)
-
- Direct Synthesis of Free α-Amino Acids by Telescoping Three-Step Process from 1,2-Diols
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A practical telescoping three-step process for the syntheses of α-amino acids from the corresponding 1,2-diols has been developed. This process enables the direct synthesis of free α-amino acids without any protection/deprotection step. This method was also effective for the preparation of a 15N-labeled α-amino acid. 1,2-Diols bearing α,β-unsaturated ester moieties afforded bicyclic α-amino acids through intramolecular [3 + 2] cycloadditions. A preliminary study suggests that the resultant α-amino acids are resolvable by aminoacylases with almost complete selectivity.
- Inada, Haruki,Shibuya, Masatoshi,Yamamoto, Yoshihiko
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supporting information
p. 709 - 713
(2019/01/25)
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- A metagenomics approach for new biocatalyst discovery: Application to transaminases and the synthesis of allylic amines
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Transaminase enzymes have significant potential for the sustainable synthesis of amines using mild aqueous reaction conditions. Here a metagenomics mining strategy has been used for new transaminase enzyme discovery. Starting from oral cavity microbiome samples, DNA sequencing and bioinformatics analyses were performed. Subsequent in silico mining of a library of contiguous reads built from the sequencing data identified 11 putative Class III transaminases which were cloned and overexpressed. Several screening protocols were used and three enzymes selected of interest due to activities towards substrates covering a wide structural diversity. Transamination of functionalized cinnamaldehydes was then investigated for the production of valuable amine building blocks.
- Baud, Damien,Jeffries, Jack W. E.,Moody, Thomas S.,Ward, John M.,Hailes, Helen C.
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p. 1134 - 1143
(2017/08/14)
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- Efficient Synthesis of CN2097 and RC7 and Their Analogs
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Synthesized macrocyclic ligand, CN2097 and analogs, optimized with systemic structure modifications to develop the compounds with lower molecular weights and less peptidic characters.
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Page/Page column
(2015/02/19)
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- Biocatalytic asymmetric synthesis of unnatural amino acids through the cascade transfer of amino groups from primary amines onto keto acids
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Flee to the hills: An unfavorable equilibrium in the amino group transfer between amino acids and keto acids catalyzed by α-transaminases was successfully overcome by coupling with a ω-transaminase reaction as an equilibrium shifter, leading to efficient asymmetric synthesis of diverse unnatural amino acids, including L-tert-leucine and D-phenylglycine. Copyright
- Park, Eul-Soo,Dong, Joo-Young,Shin, Jong-Shik
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p. 3538 - 3542
(2014/01/06)
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- Photocatalytic reversible amination of α-keto acids on a ZnS surface: Implications for the prebiotic metabolism
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We report the enzyme-like reversible amination of four intermediates pertinent to the reductive tricarboxylic acid cycle on a photo-irradiated surface of mineral sphalerite (ZnS). Given its prevalence in the waters of early Earth, we suggest that the mineral-based photochemistry might have catalyzed the homeostasis of prebiotic metabolic systems.
- Wang, Wei,Li, Qiliang,Yang, Bin,Liu, Xiaoyang,Yang, Yanqiang,Su, Wenhui
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supporting information; experimental part
p. 2146 - 2148
(2012/03/26)
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- Conductometric method for the rapid characterization of the substrate specificity of amine-transaminases
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Amine-transaminases (ATAs, ω-transaminases, ω-TA) are PLP-dependent enzymes that catalyze amino group transfer reactions. In contrast to the widespread and wellknown amino acid-transaminases, ATAs are able to convert substrates lacking an a-carboxylic functional group. They have gained increased attention because of their potential for the asymmetric synthesis of optically active amines, which are frequently used as building blocks for the preparation of numerous pharmaceuticals. Having already introduced a fast kinetic assay based on the conversion of the model substrate α-methylbenzylamine for the characterization of the amino acceptor specificity, we now report on a kinetic conductivity assay for investigating the amino donor specificity of a given ATA. The course of an ATA-catalyzed reaction can be followed conductometrically since the conducting substrates, a positively charged amine and a negatively charged keto acid, are converted to nonconducting products, a noncharged ketone and a zwitterionic amino acid. The decrease of conductivity for the investigated reaction systems were determined to be 33-52 μS mM-1. In contrast to other ATA-assays previously described, with this approach all transamination reactions between any amine and any keto add can be monitored without the need for an additional enzyme or staining solutions. The assay was used for the characterization of a ATA from Rhodobacter sphaeroides, and the data obtained were in excellent agreement with gas chromatography analysis.
- Schaetzle, Sebastian,Hoehne, Matthias,Robins, Karen,Bornscheuer, Uwe T.
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body text
p. 2082 - 2086
(2010/08/20)
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- Competing pathways in the photo-Favorskii rearrangement and release of esters: Studies on fluorinated p-hydroxyphenacyl-caged GABA and glutamate phototriggers
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(Chemical Equation Presented) Three new trifluoromethylated p-hydroxyphenacyl (pHP)-caged γ-aminobutyric acid (GABA) and glutamate (Glu) derivatives have been examined for their efficacy as photoremovable protecting groups in aqueous solution. Through the
- Stensrud, Kenneth,Noh, Jihyun,Kandler, Karl,Wirz, Jakob,Heger, Dominik,Givens, Richard S.
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scheme or table
p. 5219 - 5227
(2009/12/08)
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- Alkaloids from the mushroom pseudobaeospora pyrifera, pyriferines A-C
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Three novel alkaloids (1-3), named pyriferines A-C, were isolated from fruiting bodies of Pseudobaeospora pyrifera. They possess an unusual eight-membered N/O-acetal ring, derived from L-glutamic acid, that is connected to an enolized 1,3-diketo moiety. The structures were determined by spectroscopic methods, and the absolute configuration of the glutamic acid moiety was established using GC-MS after Mosher-type derivatization.
- Dang, Ngoc Quang,Spiteller, Peter,Porzel, Andrea,Schmidt, Juergen,Geissler, Torsten,Arnold, Norbert,Wessjohann, Ludger
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supporting information; experimental part
p. 1620 - 1622
(2009/07/03)
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- Direct introduction of glycine/mercaptoacetic acid units into electron-poor alkenes: a novel route to functionally rich α-amino/α-mercapto acids
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The first example of an operationally simple direct introduction of glycine/mercaptoacetic acid units into electron-poor alkenes is reported. In this protocol, Lewis acid-catalyzed Michael addition of activated glycine or mercaptoacetic acid, that is 2-phenyl-1,3-oxazol-5-one or 2-methyl-2-phenyl-1,3-oxathiolan-5-one, to various electron-poor alkenes in water/1,4-dioxane (1:2, v/v) solvent system diastereoselectively affords the corresponding functionally rich α-amino acids or α-mercapto acids, respectively, in high yields at ambient temperature.
- Yadav, Lal Dhar S.,Rai, Ankita
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p. 5751 - 5754
(2008/12/22)
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- Photoprocesses of molecules with 2-nitrobenzyl protecting groups and caged organic acids
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The 308 nm photoinduced formation of the nitroso product and the intermediacy of the aci-nitro form(s) were studied for a series of 2-nitrobenzyl alkyl and aryl esters (1a-4e) and bis-(nitrophenyl)methyl acetates (5a-6b) by time-resolved UV-vis spectroscopy. A triplet state appears as major transient, when 2-nitrobenzyl derivatives 1 are substituted by 4,5-dimethoxy (2) and 4,5-methylenedioxy (3/4) groups. This triplet of charge transfer character is, however, not part of the route via the aci-nitro into the 2-nitroso form. The activation energy and preexponential factor of the longest lifetime component (τaci), i.e. the major part of the aci-nitro decay, were determined. The carboxylic acids as leaving groups have rather small effects on τaci. An additional nitrated phenyl ring in α-position (5) leads generally to shorter τaci value. Otherwise, the photogeneration of nitroso products is similar. The quantum yield (Φd) varies only moderately with structure, the yield of the aci-nitro form and Φd are correlated and little affected by solvent properties.
- Bley, Filiz,Schaper, Klaus,Goerner, Helmut
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p. 162 - 171
(2008/09/18)
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- Compositions, kits, and methods relating to the human FEZ1 gene, a novel tumor suppressor gene
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The invention relates to isolated polynucleotides homologous with a portion of one strand of the human tumor suppressor gene, FEZ1, and to the tumor suppressor protein encoded thereby, Fez1. The polynucleotides are useful, for example, as probes, primers, portions of expression vectors, and the like. The invention also includes diagnostic, therapeutic, cell proliferation enhancement, and screening methods which involve these polynucleotides and protein. The invention further includes kits useful for performing the methods of the invention.
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- Synthesis and photocleavage of 7-[{Bis(carboxymethyl)amino}-coumarin-4-yl] methyl-caged neurotransmitters
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7-[{Bis(carboxymethyl)amino}coumarin-4-yl]methyl-caged neurotransmitters (glutamate and GABA) were synthesized. Both caged compounds showed sufficient stability in the dark, were water-soluble at pH 7.2 without using organic solvents, and exhibited relati
- Senda, Naoko,Momotake, Atsuya,Arai, Tatsuo
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experimental part
p. 2384 - 2388
(2009/09/08)
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- METHOD OF JUDGING LEUKEMIA, PRE-LEUKEMIA OR ALEUKEMIC MALIGNANT BLOOD DISEASE AND DIAGNOSTIC THEREFOR
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The present invention relates to a method for diagnosing leukemia, pre-leukemia or aleukemic malignant blood diseases, a method of discriminating leukemia from pre-leukemia or aleukemic malignant blood diseases, a method of discriminating aplastic anemia from myelodysplastic syndrome, a method of diagnosing delayed engraftment of the hematopoietic stem cells after transplantation of the hematopoietic stem cells, and a method of diagnosing the graft versus host disease, each of said methods comprising quantifying stem cell growth factor (SCGF). The present invention also makes it possible to provide an agent for diagnosing leukemia, pre-leukemia or aleukemic malignant blood diseases and an agent for diagnosing delayed engraftment of the hematopoietic stem cells after transplantation of the hematopoietic stem cells or an agent for diagnosing graft versus host disease (GVHD), each containing as an active ingredient an antibody reacting with stem cell growth factor (SCGF).
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- HIGH-AFFINITY INTERLEUKIN-4 MUTEINS
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A recombinant human IL-4 mutein numbered in accordance with wild-type IL-4 wherein the mutein comprises at least one amino acid substitution in the binding surface of either the A- or C-alpha helices of the wild-type IL-4 whereby the mutein binds to the IL-4R alpha receptor with at least greater affinity than native IL-4. The substitution is more preferably selected from the group of positions consisting of, in the A-helix, positions 13 and 16, and in the C-helix, positions 81 and 89. A most preferred embodiment is the recombinant human IL-4 mutein wherein the substitution at position 13 is Thr to Asp. Pharmaceutical compositions, amino acid and polynucleotide sequences encoding the muteins, transformed host cells, antibodies to the muteins, and methods of treatment are also described.
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- Small peptides having apoptotic activities and their applications
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The present invention relates to nine residue peptides (M32-40) from flavivirus M ectodomain able to modulate specifically the apoptotic activity of diverse flavivirus, to pharmaceutical composition comprising the same and their use for the treatment and/or the prevention of flavivirus-linked infections and cancers.
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- Process for producing alpha 2,3/ alpha 2,8-sialyltransferase and sialic acid-containing complex sugar
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The present invention can provide a process for producing a protein having α2,3/α2,8-sialyltransferase activity using a transformant comprising a DNA encoding a protein having α2,3/α2,8-sialyltransferase activity derived from a microorganism belonging to the genus Pasteurella and a process for producing a sialic acid-containing complex carbohydrate using a transformant capable of producing a protein having α2,3/α2,8-sialyltransferase activity derived from a microorganism.
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- Novel protein and use thereof
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A novel gene likely inhibiting the onset and progress of cancer. A protein having an amino acid sequence which is the same or substantially the same as the amino acid sequence represented by SEQ ID NO:4 or its salt; a polynucleotide encoding the same; and medicinal use, etc. thereof are provided.
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- CIS-ELEMENT REGULATING TRANSCRIPTION, TRANSCRIPTIONAL REGULATORY FACTOR BINDING SPECIFICALLY THERETO AND USE OF THE SAME
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The present invention provides a novel fructose responsive transcription control cis-element and a transcriptional regulatory factor that interacts therewith, a non-human animal having them transferred or inactivated, a diagnostic method for genetic susceptibility to a metabolic disorder using them, and a screening method for a prophylactic or therapeutic drug for a metabolic disorder using them.
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- Interleukin-2:remodeling and glycoconjugation of interleukin-2
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The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
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- T-CELL SELECTIVE INTERLEUKIN-4 AGONISTS
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The invention is directed to human IL-4 muteins numbered in accordance with wild-type IL-4 having T-cell activating activity, but having reduced endothelial cell activating activity. In particular, the invention is related to human IL-4 muteins wherein the surface-exposed residues of the D helix of the wild-type IL-4 are mutated whereby the resulting mutein causes T-cell proliferation, and causes reduced IL-6 secretion from HUVECs, relative to wild-type IL-4. This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of this interleukin. Further, the invention is directed to IL-4 muteins having single, double and triple mutations represented by the designators R121A, R121D, R121E, R121F, R121H, R121I, R121K, R121N, R121P, R121T, R121W; Y124A, Y124Q, Y124R, Y124S, Y124T; Y124A/S125A, T13D/R121E; and R121T/E122F/Y124Q, when numbered in accordance with wild-type IL-4 (His=1). The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.
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- CONJUGATES OF TRANSPORTER PEPTIDES AND NUCLEIC ACID ANALOGS, AND THEIR USE
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Constructs of peptides and nucleic acid analogs conjugated together for transport across a lipid membrane and for delivery into interactive contact with intracellular polynucleotides are disclosed. Transport is effected through at least the exterior membrane of a cell, and most likely also through the walls of subcellular structures separated from the cytosol by lipid membranes, including the nucleus, mitochondria, ribosomes, etc. Peptide nucleic acid (PNA) analog sequences conjugated through a labile disulfide bond to transporting peptides, are intracellulary cleaved, and target mRNA (antigene) or dsDNA (antisense).
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- Porcine retrovirus
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The present invention provides porcine retrovirus (PoEV) polynucleotide fragments, particularly those encoding at least one PoEV expression product, a recombinant vector comprising such a polynucleotide fragment or fragments, use of PoEV polynucleotide fragments in the detection of native PoEV, a host cell containing at least one PoEv polynucleotide fragment or recombinant vector, PoEV polypeptides, antibodies immuno-reactive with PoEV polypeptides, pharmaceutical compositions comprising recombinant PoEV polypeptides for use as prophylactic and/or therapeutic agents and uses of PoEV polynucleotide fragments and/or polypeptides in medicine, including veterinary medicine and in the preparation of medicaments for use in medicine.
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- Protein interaction method and composition
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A protein interaction method and composition are described. The method and composition are useful for a number of purposes including: reconstituting multisubunit protein complexes, identifying known binding subunits, determining the kinetics and order of self assembly of a multisubunit protein complex, and drug screening. The method involves contacting a conjugate with a solid surface having an immobilized first coil-forming peptide characterized by a selected charge and an ability to interact with a second, oppositely charged coil-forming peptide to form a stable α-helical coiled-coil heterodimer, where the conjugate comprises (a) the second, oppositely charged coil-forming peptide, and (b) a first subunit polypeptide which is one of a plurality of subunit polypeptides in a multisubunit complex. By said contacting the conjugate is bound to the solid surface. Other subunits of the complex are added under conditions effective to promote self-assembly of the subunit complex on the solid surface.
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- Treatment of HIV-associated dysmorphia/dysmetabolic syndrome (HADDS) with or without lipodystrophy
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Pathological regional adipose tissue accumulation associated with HIV-associated dysmorphic/dysmetabolic syndrome (HADDS) which may occur with or without subcutaneous adipose tissue lipodystrophy (and which is also described as HIV-associated adipose redistribution syndrome or HARS and other specific medical terms), is treated by administering an effective amount of human growth hormone or other substance which binds to and initiates signalling of the hGH receptor. Alternatively, a substance which stimulates production of endogenous hGH, such as human growth hormone releasing hormone, may be administered. HADDS and related syndromes include abnormal adipose tissue accumulation in the visceral, submandibular, supraclavicular, pectoral, mammary and/or dorsocervical (buffalo hump) area, and/or with subcutaneous lipomas, with or without associated metabolic or other physiologic abnormalities.
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- Insulin analogs with enhanced zinc binding
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The invention relates to insulin analogs exhibiting enhanced zinc binding capacity and to stable zinc complexes thereof having a retarded activity in comparison with human insulin. The invention further relates to a method for the production of said insulin analogs and to their use, particularly in pharmaceutical preparations for therapy of type I and type II diabetes mellitus.
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- Methods and compositions for controlled polypeptide synthesis
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Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for initiating the polymerization of aminoacid-N-carboxyanhydride (NCA) monomer by combining the monomer with an amido-containing metallacycle, for making self assembling amphiphilic block copolypeptides and related protocols for adding oligo(ethyleneglycol) functionalized aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex to forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.
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- Active agent delivery systems and methods for protecting and administering active agents
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The present invention relates to active agent delivery systems and more specifically to compositions that comprise amino acids, as single amino acids or peptides, covalently attached to active agents and methods for administering conjugated active agent compositions.
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- ATTENUATED FLAVIVRUS STRAINS CONTAINING A MUTATED M-ECTODOMAIN AND THEIR APPLICATIONS
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The present invention relates to nine residue peptides (ApoptoM) from flavivirus M ectodomain able to modulate specifically the apoptotic activity of diverse flavivirus, to pharmaceutical composition comprising the same and their use for the treatment and/or the prevention of flavivirus-linked infections and cancers.
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- Novel G protein-coupled receptor protein, its DNA and ligand thereof
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The polypeptides in the present invention possess the effects of promoting and inhibiting the secretion of prolactin, and are thus useful as drugs for the prevention and treatment of various diseases, in terms of prolactin secretion stimulants, which are associated with the secretion of prolactin, such as hypoovarianism, spermatic underdevelopment, menopausal symptoms, hypothyroidism, etc. The polypeptides are useful as drugs for the prevention and treatment of various diseases, in terms of prolactin secretion inhibitors, which are associated with the secretion of prolactin, such as pituitary tumor, diencephalon tumor, menstrual disorder, autoimmune diseases, prolactinoma, sterility, impotence, amenorrhea, lactorrhea, acromegaly, Chiari-Frommel syndrome, Argonz-del Castilo syndrome, Forbes-Albright syndrome, lymphoma, Sheehan's syndrome, spermatogenesis disorder, etc.
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- Mst1 modulation of apoptosis in cardiac tissue and modultors of Mst1 for treatment and prevention of cardiac disease
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The present invention relates to methods and agents for treatment, amelioration and prevention of cardiac disease, including cardiac myopathy, chronic heart failure and for management and reduction of cardiac myocyte death which may occur in response to ischemia/reperfusion or following myocardial infarction or other injury to the heart. The invention relates to methods for screening cardiotherapeutic compounds, including compounds which modulate cardiac myocyte apoptosis, particularly targeting Mst1 and the Mst1 pathway. The present invention further encompasses compounds identified by such screening methods and compositions comprising these compounds. The invention also provides methods for treatment, amelioration and prevention of cardiac disease comprising administering compounds or agents which modulate, particularly inhibit, Mst1 or the Mst1 kinase pathway, including administering a nucleic acid encoding an altered form of Mst1, particularly a dominant negative Mst1, which acts as an antagonist of Mst1.
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- Production of sulfated polysaccharides using glycosaminoglycan-specific sulfotransferases
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The present invention provides materials and methods for the production of bifunctional enzymes that catalyze the N-deacetylation and N-sulfation of saccharides. The invention also provides conditions and methods for assaying the activity of such enzymes.
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- Protein remodeling methods and proteins/peptides produced by the methods
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The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
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- Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF
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The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
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- Interferon alpha: remodeling and glycoconjugation of interferon alpha
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The invention includes a multitude of methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
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- Compositions and methods for promoting internalization and degradation of urokinase-type plasminogen activator
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The invention includes compositions and methods for promoting internalization and degradation of urokinase-type plasminogen activator.
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- Interferon beta: remodeling and glycoconjugation of interferon beta
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The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
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- Glycoconjugation methods and proteins/peptides produced by the methods
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The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
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- Therapeutic and diagnostic methods and compositions based on jagged/notch proteins and nucleic acids
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This invention relates to therapeutic and diagnostic methods and compositions based on Jagged/Notch proteins and nucleic acids, and on their role in the signaling pathway relating to endothelial cell migration and/or differentiation. In addition, this invention provides a substantially purified Jagged protein, as well as a substantially purified nucleic acid or segment thereof encoding Jagged protein, or a functionally equivalent derivative, or allelic or species variant thereof. Further, this invention provides a substantially purified soluble Jagged protein and a substantially purified nucleic acid encoding same as well as a recombinant cell comprising a nucleic acid encoding a soluble Jagged protein. Soluble Jagged provides further therapeutic and diagnostic methods relating to diseases, disorders, and conditions involving Jagged/Notch signaling including, inter alia, angiogenesis, differentiation, and control of gene expression.
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- Method of treating cancer
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The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and a glucocorticoid, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least one PSA conjugate and at least one glucocorticoid. The invention also relates to methods of preparing such compositions.
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- pH-Dependent Chemoselective Synthesis of α-Amino Acids. Reductive Amination of α-Keto Acids with Ammonia Catalyzed by Acid-Stable Iridium Hydride Complexes in Water
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An acid-stable hydride complex [Cp*IrIII(bpy)H]+ {1, Cp* = η5-C5Me5, bpy = 2,2′-bipyridine} serves as the active catalyst for the highly chemoselective synthesis of α-amino acids by reductive aminatio
- Ogo, Seiji,Uehara, Keiji,Abura, Tsutomu,Fukuzumi, Shunichi
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p. 3020 - 3021
(2007/10/03)
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- Compounds that bind HER2
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The invention provides novel compounds which bind to the human erbB2 gene product (ErbB2, also known as HER2, or c-ErbB-2). In particular aspects, the invention provides for the treatment of disorders characterized by the overexpression of ErbB2 utilizing the novel compounds of the invention. The invention also provides pharmaceutical compositions comprising the novel compounds as well as for their use in research, diagnostic, therapeutic, and prophylactic methods.
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- Egg specific surface proteins
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The present invention relates to proteins that are expressed in oocytes, nucleic acid sequences encoding those proteins and antibodies generated against those proteins. Composition and methods are provided for using the disclosed oocyte proteins as targets for contraceptive drugs.
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- Carbohydrate epitope mimic compounds and uses thereof
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This invention provides carbohydrate epitope mimic compounds, particularly peptides, and analogs and variants thereof. In particular, the compounds and peptides of the present invention mimic the carbohydrate epitope GlcAβ1→3Galβ1→4GlcNAc or sulfate -3GlcAβ1→3Galβ1→4GlcNAc, or the L2/HNK1 carbohydrate epitope. This invention provides an isolated peptide comprising an amino acid sequence of a carbohydrate epitope mimic peptide in which the amino acid sequence is set forth in any of SEQ ID NOS: 1-8, 27-38, 39, 40 and 41, including variants, analogs and active fragments thereof. The invention further provides an isolated nucleic acid encoding a peptide comprising an amino acid sequence of a carbohydrate epitope mimic peptide. This invention provides pharmaceutical compositions and diagnostic and therapeutic methods of use of the isolated polypeptides and nucleic acids, particularly in modulating or mediating cell-cell adhesion and viral infection and the processes and events mediated thereby. Assays for compounds which mimic, alter or inactivate the polypeptides of the present invention for use in therapy are also provided.
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- Inhibition of BEHAB cleavage and primary central nervous system (CNS) tumors
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The present invention relates to primary CNS tumors and provides useful compositions and methods for reducing tumor volume and increasing the length of survival in mammals with primary CNS tumors, thereby providing a treatment for primary CNS tumors. The invention also relates to methods of identifying compounds for reducing tumor volume and increasing animal survival, which therefore relate to treating primary CNS tumors.
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- Compositions, methods, and kits relating to resistin-like molecules
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The invention relates to novel nucleic acids encoding a mammalian resistin-like molecule (RELM), and proteins encoded thereby, whose expression is increased in certain diseases, disorders, or conditions, including, but not limited to, intestinal (e.g., colonic) tumors. The invention further relates to methods of treating and detecting irritable bowel disease, inflammatory bowel disease, familial adenomatous polyposis, diabetes, insulin resistance, obesity, Syndrome X, and glucose metabolism disorders, colon cancer, breast cancer, and tongue cancer, comprising modulating or detecting RELM expression and/or production and activity of RELM polypeptide, wherein RELM encompasses resistin-like molecule α and resistin-like molecule β.
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- Mammalian prestin polynucleotides
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The invention relates to mammalian prestin protein, which has been discovered to be the mammalian cochlear outer hair cell motor, and to polynucleotides encoding prestin. Full length gerbil prestin and its cDNA are described, full length murine prestin and its cDNA are described, and a partial sequence of human prestin and its chromosomal location are described.
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- Methods and compositions for controlled polypeptide synthesis
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Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for making self assembling amphiphilic block copolypeptides and related protocols adding oligo(ethyleneglycol) functionalized aninoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex, thereby forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.
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