- Rational engineering ofAcinetobacter tandoiiglutamate dehydrogenase for asymmetric synthesis ofl-homoalanine through biocatalytic cascades
-
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
-
p. 4208 - 4215
(2021/06/30)
-
- Decarboxylative Radical Addition to Methylideneoxazolidinones for Stereocontrolled Synthesis of Selectively Protected Diamino Diacids
-
Syntheses of stereochemically pure and selectively protected diamino diacids can be achieved by redox decarboxylation of distal N-hydroxyphthalimide esters of protected aspartic, glutamic or α-aminoadipic acids via radical addition to methylideneoxazolidinones. The products are useful for solid-supported syntheses of robust bioactive carbocyclic peptide analogs. Yields of reactive primary radical addition are superior to those of more stabilized radicals, and the reaction fails if the alkylideneoxazolidinone has a methyl substituent on its terminus (i.e., 13a/13b).
- Annadate, Ritesh,Beadle, Jonathan,Hsiao, Yu-Ting,Pascoe, Cameron,Vederas, John C.
-
supporting information
p. 7270 - 7273
(2021/10/01)
-
- Synthesis of Unprotected 2-Arylglycines by Transamination of Arylglyoxylic Acids with 2-(2-Chlorophenyl)glycine
-
The transamination of α-keto acids with 2-phenylglycine is an effective methodology for directly synthesizing unprotected α-amino acids. However, the synthesis of 2-arylglycines by transamination is problematic because the corresponding products, 2-arylglycines, transaminate the starting arylglyoxylic acids. Herein, we demonstrate the use of commercially available l-2-(2-chlorophenyl)glycine as the nitrogen source in the transamination of arylglyoxylic acids, producing the corresponding 2-arylglycines without interference from the undesired self-transamination process.
- Inada, Haruki,Shibuya, Masatoshi,Yamamoto, Yoshihiko
-
p. 11047 - 11059
(2020/10/12)
-
- Highly Efficient Synthesis of Amino Acids by Amination of Bio-Derived Hydroxy Acids with Ammonia over Ru Supported on N-Doped Carbon Nanotubes
-
The amino acids have extensive applications, and their productions from biomass-derived feedstocks are very attractive. In this work, the synthesis of amino acids by amination of bio-derived hydroxy acids with ammonia over different metallic nano-catalysts supported on various supports is studied. It is found that Ru nano-catalysts on the nitrogen-doped carbon nanotubes (Ru/N?CNTs) have an outstanding performance for the reaction. Different hydroxy acids can be catalytically converted into the corresponding amino acids with yields up to 70.0 % under mild conditions, which is higher than those reported. The reasons for the high efficiency of the catalyst are investigated, and the reaction pathway is proposed on the basis of control experiments.
- Xie, Zhenbing,Chen, Bingfeng,Peng, Fangfang,Liu, Mingyang,Liu, Huizhen,Yang, Guanying,Han, Buxing
-
p. 5683 - 5689
(2020/09/21)
-
- Direct Synthesis of Free α-Amino Acids by Telescoping Three-Step Process from 1,2-Diols
-
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
-
supporting information
p. 709 - 713
(2019/01/25)
-
- Electrosynthesis of amino acids from biomass-derivable acids on titanium dioxide
-
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
-
supporting information
p. 14721 - 14724
(2019/12/24)
-
- Organocatalytic Enantioselective Addition of α-Aminoalkyl Radicals to Isoquinolines
-
With a dual organocatalytic system involving a chiral phosphoric acid and a dicyanopyrazine-derived chromophore (DPZ) photosensitizer and under the irradiation with visible light, an enantioselective Minisci-type addition of α-amino acid-derived redox-active esters (RAEs) to isoquinolines has been developed. A variety of prochiral α-aminoalkyl radicals generated from RAEs were successfully introduced on isoquinolines, providing a range of valuable α-isoquinoline-substituted chiral secondary amines in high yields with good to excellent enantioselectivities.
- Liu, Xiangyuan,Liu, Yang,Chai, Guobi,Qiao, Baokun,Zhao, Xiaowei,Jiang, Zhiyong
-
supporting information
p. 6298 - 6301
(2018/10/09)
-
- Catalytic amino acid production from biomass-derived intermediates
-
Amino acids are the building blocks for protein biosynthesis and find use in myriad industrial applications including in food for humans, in animal feed, and as precursors for bio-based plastics, among others. However, the development of efficient chemical methods to convert abundant and renewable feedstocks into amino acids has been largely unsuccessful to date. To that end, here we report a heterogeneous catalyst that directly transforms lignocellulosic biomass-derived α-hydroxyl acids into α-amino acids, including alanine, leucine, valine, aspartic acid, and phenylalanine in high yields. The reaction follows a dehydrogenation-reductive amination pathway, with dehydrogenation as the rate-determining step. Ruthenium nanoparticles supported on carbon nanotubes (Ru/CNT) exhibit exceptional efficiency compared with catalysts based on other metals, due to the unique, reversible enhancement effect of NH3 on Ru in dehydrogenation. Based on the catalytic system, a two-step chemical process was designed to convert glucose into alanine in 43% yield, comparable with the well-established microbial cultivation process, and therefore, the present strategy enables a route for the production of amino acids from renewable feedstocks. Moreover, a conceptual process design employing membrane distillation to facilitate product purification is proposed and validated. Overall, this study offers a rapid and potentially more efficient chemical method to produce amino acids from woody biomass components.
- Deng, Weiping,Wang, Yunzhu,Zhang, Sui,Gupta, Krishna M.,Hülsey, Max J.,Asakura, Hiroyuki,Liu, Lingmei,Han, Yu,Karp, Eric M.,Beckham, Gregg T.,Dyson, Paul J.,Jiang, Jianwen,Tanaka, Tsunehiro,Wang, Ye,Yan, Ning
-
p. 5093 - 5098
(2018/05/23)
-
- PROCESS FOR THE RACEMIZATION OF ALPHA-AMINO ACIDS
-
According to the present invention, a method is provided wherein a basic aqueous phase containing an optically active α-amino acid is brought into contact with an organic phase containing a racemisation catalyst in the form of a copper metal complex of copper ions and an α-amino acid and salicylaldehyde, in the presence of a phase transition catalyst, thereby subjecting the optically active α-amino acid to racemisation. In the α-amino acid racemisation method according to the present invention, the reaction conditions are mild and thus there is little α-amino acid breakdown and the yield is high, the racemisation catalyst can be reused, the α-amino acid resulting from the racemisation can easily be isolated and purified, and the racemisation method can be implemented in volume such that the invention is economic.
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Paragraph 0086-0087
(2016/08/29)
-
- A method for preparing DL-leucine (by machine translation)
-
The invention discloses a method for preparing DL-leucine. The method of the invention first through ethanol, acetamide, ethanol sodium and isobutyl bromide reaction, reaction solution distillation recovery ethanol, distillation residues hot-melt, filtering, cooling to crystallize, shall be 2-isobutyl-acetamide; and then the 2-isobutyl-acetamide react with sodium hypochlorite, reaction solution distillation recovery chcl, distillation residual the toluene-P-sulfonic acid reaction, the reaction liquid filtering, cooling to crystallize, shall be leucine paratoluene sulfonic acid; leucines toluene-P-sulfonic acid with sodium hydroxide reaction, and the re-adjustment to pH 6-6.5 DL-leucine can be obtained. The invention chemical synthetic mild reaction conditions, the low requirements for the equipment, production cycle is short, with little investment, low cost; relatively high yield, there are few by-products, can be produced in large quantities, which is beneficial for industrial; acetamide can be formed by preparing ketene dimer, easily available raw materials. (by machine translation)
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-
Paragraph 0011
(2017/03/14)
-
- General Synthesis of Amino Acid Salts from Amino Alcohols and Basic Water Liberating H2
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An atom-economical and environmentally friendly method to transform amino alcohols to amino acid salts using just basic water, without the need of pre-protection or added oxidant, catalyzed by a ruthenium pincer complex, is developed. Water is the solvent, the source of the oxygen atom of the carboxylic acid group, and the actual oxidant, with liberation of dihydrogen. Many important and useful natural and unnatural amino acid salts can be produced in excellent yields by applying this new method.
- Hu, Peng,Ben-David, Yehoshoa,Milstein, David
-
supporting information
p. 6143 - 6146
(2016/06/09)
-
- 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)
-
- Identification of four new agr quorum sensing-interfering cyclodepsipeptides from a marine Photobacterium
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During our search for new natural products from the marine environment, we discovered a wide range of cyclic peptides from a marine Photobacterium, closely related to P. halotolerans. The chemical fingerprint of the bacterium showed primarily non-ribosomal peptide synthetase (NRPS)-like compounds, including the known pyrrothine antibiotic holomycin and a wide range of peptides, from diketopiperazines to cyclodepsipeptides of 500-900 Da. Purification of components from the pellet fraction led to the isolation and structure elucidation of four new cyclodepsipeptides, ngercheumicin F, G, H, and I. The ngercheumicins interfered with expression of virulence genes known to be controlled by the agr quorum sensing system of Staphylococcus aureus, although to a lesser extent than the previously described solonamides from the same strain of Photobacterium.
- Kjaerulff, Louise,Nielsen, Anita,Mansson, Maria,Gram, Lone,Larsen, Thomas O.,Ingmer, Hanne,Gotfredsen, Charlotte H.
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p. 5051 - 5062
(2014/02/14)
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- Meteorites as catalysts for prebiotic chemistry
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From outer space: Twelve meteorite specimens, representative of their major classes, catalyse the synthesis of nucleobases, carboxylic acids, aminoacids and low-molecular-weight compounds from formamide (see figure). Different chemical pathways are identified, the yields are high for a prebiotic process and the products come in rich and composite panels.
- Saladino, Raffaele,Botta, Giorgia,Delfino, Michela,Di Mauro, Ernesto
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p. 16916 - 16922
(2014/01/06)
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- Boron-doped diamond electrodes for the electrochemical oxidation and cleavage of peptides
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Electrochemical oxidation of peptides and proteins is traditionally performed on carbon-based electrodes. Adsorption caused by the affinity of hydrophobic and aromatic amino acids toward these surfaces leads to electrode fouling. We compared the performance of boron-doped diamond (BDD) and glassy carbon (GC) electrodes for the electrochemical oxidation and cleavage of peptides. An optimal working potential of 2000 mV was chosen to ensure oxidation of peptides on BDD by electron transfer processes only. Oxidation by electrogenerated OH radicals took place above 2500 mV on BDD, which is undesirable if cleavage of a peptide is to be achieved. BDD showed improved cleavage yield and reduced adsorption for a set of small peptides, some of which had been previously shown to undergo electrochemical cleavage C-terminal to tyrosine (Tyr) and tryptophan (Trp) on porous carbon electrodes. Repeated oxidation with BDD electrodes resulted in progressively lower conversion yields due to a change in surface termination. Cathodic pretreatment of BDD at a negative potential in an acidic environment successfully regenerated the electrode surface and allowed for repeatable reactions over extended periods of time. BDD electrodes are a promising alternative to GC electrodes in terms of reduced adsorption and fouling and the possibility to regenerate them for consistent high-yield electrochemical cleavage of peptides. The fact that OH-radicals can be produced by anodic oxidation of water at elevated positive potentials is an additional advantage as they allow another set of oxidative reactions in analogy to the Fenton reaction, thus widening the scope of electrochemistry in protein and peptide chemistry and analytics.
- Roeser, Julien,Alting, Niels F. A.,Permentier, Hjalmar P.,Bruins, Andries P.,Bischoff, Rainer
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p. 6626 - 6632
(2013/08/23)
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- A new acylamidase from Rhodococcus erythropolis TA37 can hydrolyze N-substituted amides
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A new acylamidase was isolated from Rhodococcus erythropolis TA37 and characterized. N-Substituted acrylamides (isopropyl acrylamide, N,N-dimethyl-aminopropyl acrylamide, and methylene-bis-acrylamide), acid para-nitroanilides (4′-nitroacetanilide, Gly-pNA, Ala-pNA, Leu-pNA), and N-acetyl derivatives of glycine, alanine, and leucine are good substrates for this enzyme. Aliphatic amides (acetamide, acrylamide, isobutyramide, n-butyramide, and valeramide) are also used as substrates but with less efficiency. The enzyme subunit mass by SDS-PAGE is 55 kDa. Maximal activity is exhibited at pH 7-8 and 55°C. The enzyme is stable for 15 h at 22°C and for 0.5 h at 45°C. The Michaelis constant (K m) is 0.25 mM with Gly-pNA and 0.55 mM with Ala-pNA. The acylamidase activity is suppressed by inhibitors of serine proteases (phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate) but is not suppressed by inhibitors of aliphatic amidases (acetaldehyde and nitrophenyl disulfides). The N-terminal amino acid sequence of the acylamidase is highly homologous to those of two putative amidases detected from sequenced R. erythropolis genomes. It is suggested that the acylamidase together with the detected homologs forms a new class within the amidase signature family.
- Lavrov,Zalunin,Kotlova,Yanenko
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experimental part
p. 1006 - 1013
(2011/11/06)
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- New C14-surfactin methyl ester from the marine bacterium Bacillus pumilus KMM 456
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New C14-surfactin methyl ester and eight earlier described surfactins were isolated from the marine bacterium Bacillus pumilus associated with zoantharia Palythoa sp. The structure of the compounds isolated was established based on the data from amino acid analysis, one- and two-dimensional NMR spectroscopy, and tandem nanoelectrospray mass spectrometry. The absolute configurations of amino acids were determined by Marfey's method. Cytotoxic activity of a number of surfactins with respect to the tumor cells HCT-116 and MDA-MB-231 was studied.
- Zhuravleva,Afiyatullov,Ermakova,Nedashkovskaya,Dmitrenok,Denisenko,Kuznetsova
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experimental part
p. 2137 - 2142
(2011/08/04)
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- Constituents of Zizyphus jujuba
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Three flavonoids, kaempferol-7-methylether, kaempferol and myrecetin together with a cyclopeptide alkaloid, nummularine-K have been isolated from the barks of Zizyphus jujuba and their structures established by spectral evidences. This is the first report of occurrence of these compounds in Z. jujuba.
- Pandey,Singh,Singh, Sarita,Singh
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experimental part
p. 555 - 556
(2009/07/18)
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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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- 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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- 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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- 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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- Process for producing beta-1, 3-n-acetylglucosamine transferase and n-acetylglucosamine- containing composite saccharide
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The present invention can provide a process for producing a protein having β1,3-N-acetylglucosaminyltransferase activity using a transformant comprising a DNA encoding a protein having β1,3-N-acetylglucosaminyltransferase activity derived from a microorganism belonging to the genus Pasteurella and a process for producing an N-acetylglucosamine-containing complex carbohydrate using a transformant capable of producing a protein having β1,3-N-acetylglucosaminyltransferase activity derived from a microorganism.
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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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- 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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- 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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- 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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- Inhalable sustained therapeutic formulations
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The present invention is based, in part, on the unexpected discovery that particles for pulmonary delivery of a therapeutic, prophylactic or diagnostic agent that comprise a phospholipid and a sufficient amount of leucine can produce sustained effect of the agent. Specifically, particles for pulmonary delivery of a therapeutic, prophylactic or diagnostic agent that contain a phospholipid or combination of phospholipids, wherein the phospholipid or combination of phospholipids is present in the particles in an amount of about 1 to 46 weight percent; and leucine, wherein leucine is present in the particles in an amount of at least 46 weight percent, can contribute to sustained effect of the agent. Particles that comprise at least 46 weight percent leucine but that do not contain phospholipids do not exhibit these same sustained effect properties.
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- Alpha-glycated amino acid releasing enzyme
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The present invention relates to a novel enzyme (α-GARE) which releases an amino acid residue having a glycated α-amino group (α-GA) from a glycated protein etc. and to bacterial strains producing the same. Examples of the bacterial strains include Sphingomonas parapaucimobilis KDK1004 (FERM BP-7041). The α-GARE is contained in the culture supernatant of this strain and α-GA can be released from a glycated peptide by using the same, as shown in FIG. 1.
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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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- Inhibitors of the E2F-1/cyclin interaction for cancer therapy
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The novel compounds of this invention have the general structural formula Ia-d: The compounds of this invention relate to 8-mer, 7-mer, 6-mer and 5-mer peptides having the following amino acid sequences, and referred to collectively as having “Formula Ia-d”: Cap-AA8-AA7-AA6-AA5-AA4*-AA3-AA2-AA1*8-merIaCap-AA7-AA6-AA5-AA4*-AA3-AA2-AA1*7-merIbCap-AA6-AA5-AA4*-AA3-AA2-AA1*6-merIcCap-AA5-AA4*-AA3-AA2-AA1*5-merId or a pharmaceutically acceptable salt or ester thereof, that inhibit the interaction of the transcription factor E2F-1 to Cyclin A. As an antagonist of the E2F-1/Cyclin A interaction, the compounds of the present invention may be used in the treatment of cancer.
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- Inhibitors of the E2F-1/cyclin interaction for cancer therapy
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The novel compounds of this invention have the general structural formula Ia-d: The compounds of this invention relate to 8-mer, 7-mer, 6-mer and 5-mer peptides having the following amino acid-sequences, and referred to collectively as having “Formula Ia-d”: Cap-AA8-AA7-AA6-AA5-AA4*-AA3-AA2-AA1*8-merlaCap-AA7-AA6-AA5-AA4*-AA3-AA2-AA1*7-merlbCap-AA6-AA5-AA4*-AA3-AA2-AA1*6-merlcCap-AA5-AA4*-AA3-AA2-AA1*5-merld or a pharmaceutically acceptable salt or ester thereof, that inhibit the interaction of the transcription factor E2F-1 to Cyclin A. As an antagonist of the E2F-1/Cyclin A interaction, the compounds of the present invention may be used in the treatment of cancer.
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- Split- ubiquitin based reporter systems and methods of their use
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Methods and reagents for the detection and selection of two interacting-polypeptides, especially integral membrane proteins and transcription factors, by monitoring the reassembly of ubiquitin amino-terminal and carboxy-terminal chimeric polypeptide fragments are disclosed. Negative selection against an N-end rule-labilized marker released following ubiquitin reassembly allows direct selection of the interacting polypeptide pair. Methods to identify agonists and antagonists for certain protein-protein interactions; methods and reagents/kits for identifying proteins that binds a target protein are also provided. The dynamic and adaptable nature of the assay allows adaptation to a number of applications—such as probing the molecular environment of cellular membrane proteins in vivo.
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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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- Beta1, 3-galactose transferase and dna encoding the enzyme
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The present invention provides a protein having β1,3-galactosyltransferase activity, a DNA encoding the protein, a transformant comprising the DNA, a process for producing the protein using the transformant, and a process for producing a galactose-containing complex carbohydrate using the transformant.
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- Process for producing alpha1,4-galactosyltransferase and galactose-containing complex sugar
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The present invention can provide a process for producing a protein having α1.4-galactosyltransferase activity using a transformant comprising a DNA encoding a protein having α1.4-galactosyltransferase activity derived from a microorganism belonging to the genus Pasteurella and a process for producing a galactose-containing complex carbohydrate using a transformant capable of producing a protein having α1,4-galactosyltransferase activity derived from a microorganism.
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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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- 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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