- A new simple preparation of D-alloisoleucine suitable for large-scale manufacture
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D-Alloisoleucine (D-aIle) was obtained by the resolution of the epimer mixture of L-isoleucine (L-Ile) and D-aIle, which was formed by epimerization of L-Ile, with a resolving agent such as (2S,3S)-dibenzoyltartaric acid ((2S,3S)-DBTA) or (2S,3S)-di-4-toluoyl-tartaric acid ((2S,3S)-DTTA).
- Noda, Hirofumi,Sakai, Kenichi,Murakami, Hisamichi
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Read Online
- A simple preparation of d-alloisoleucine from l-isoleucine via acetylation and separation of the ammonium salts
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d-Alloisoleucine was obtained from l-isoleucine by acetylation and epimerization by acetic anhydride followed by separation of the diastereoisomeric ammonium salts using the solubility difference. The structure-solubility relationship of diastereoisomeric salts was explained by X-ray crystal structure analysis.
- Yajima, Tatsuo,Horikawa, Takao,Takeda, Nobuhiro,Takemura, Eri,Hattori, Hiroaki,Shimazaki, Yuichi,Shiraiwa, Tadashi
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Read Online
- New compounds from a hydrothermal vent crab-associated fungus Aspergillus versicolor XZ-4
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Three new quinazoline derivatives (1-3), one new oxepin-containing natural product (4) and four new cyclopenin derivatives (5-7 and 9) have been isolated from an EtOAc extract of the Taiwan Kueishantao hydrothermal vent crab-associated fungus Aspergillus versicolor XZ-4. Their planar structures were established by HRMS, 1D and 2D NMR spectroscopic data analyses. The absolute configurations for compounds 1 and 4 were determined by chiral phase HPLC analysis of their hydrolysis products. The absolute configurations of 2, 3 and 7 were defined mainly by comparison of the quantum chemical TDDFT calculated and the experimental ECD spectra, and the absolute configuration of 5 was deduced from comparison of the optical rotation values reported in the literature. The presence of two atropisomers of 5 was established by NOE analyses. The Ile & Val units in compounds 1-3 allowed the assignment of a new quinazoline skeleton and it's the first time the configuration of isoleucine in the quinazoline skeleton was defined. A series of 7-methoxy cyclopenin derivatives were reported for the first time in this study. The bioevaluation of compounds 5, 7, 8 and 9 revealed inhibitory activities against E. coli at MIC values around 32 μg mL?1
- Pan, Chengqian,Shi, Yutong,Chen, Xuegang,Chen, Chen-Tung Arthur,Tao, Xinyi,Wu, Bin
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- Racemisation of Activated, Urethane-protected Amino-acids by p-Dimethylaminopyridine. Significance in Solid-phase Peptide Synthesis
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Racemisation of Nα-t-butoxycarbonyl, fluoren-9-ylmethoxycarbonyl, and benzyloxycarbonyl amino-acid anhydrides by p-dimethylaminopyridine is shown to be a significant side reaction during attachment of the first amino-acid to the resin in solid-phase peptide synthesis.
- Atherton, Eric,Benoiton, N. Leo,Brown, Evelyn,Sheppard, Robert C.,Williams, Brian J.
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Read Online
- Polyketides, diketopiperazines and an isochromanone from the marine-derived fungal strain Fusarium graminearum FM1010 from Hawaii
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The fungal strain Fusarium graminearum FM1010 was isolated from a shallow-water volcanic rock known as “live rock” at the Carl Smith Beach, Hilo, Hawaii. Eleven specialised metabolites, including two undescribed diketopiperazines, three undescribed polyketides, and one undescribed isochromanone, along with five known fusarielin derivatives were obtained from F. graminearum FM1010. The structures of the six undescribed compounds were elucidated by extensive analysis of NMR spectroscopy, HRESIMS, chemical reactions, and electronic circular dichroism (ECD) data. Kaneoheoic acids G-I showed mild inhibitory activity against S. aureus with the MIC values in the range of 20–40 μg/mL when assayed in combination with chloramphenicol (half of the MIC, 1 μg/mL), an FDA approved antibiotic. Kaneoheoic acid I exhibited both anti-proliferative activity against ovarian cancer cell line A2780 and TNF-α induced NF-κB inhibitory activity with the IC50 values of 18.52 and 15.86 μM, respectively.
- Cao, Shugeng,Sarotti, Ariel M.,Uz Zaman, KH Ahammad,Wu, Xiaohua
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- 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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- 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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- Discovery of new A- and B-type laxaphycins with synergistic anticancer activity
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Two new cyclic lipopeptides termed laxaphycins B4 (1) and A2 (2) were discovered from a collection of the marine cyanobacterium Hormothamnion enteromorphoides, along with the known compound laxaphycin A. The planar structures were solved based on a combined interpretation of 1D and 2D NMR data and mass spectral data. The absolute configurations of the subunits were determined by chiral LC-MS analysis of the hydrolysates, advanced Marfey's analysis and 1D and 2D ROESY experiments. Consistent with similar findings on other laxaphycin A- and B-type peptides, laxaphycin B4 (1) showed antiproliferative effects against human colon cancer HCT116 cells with IC50 of 1.7 μM, while laxaphycins A and A2 (2) exhibited weak activities. The two major compounds isolated from the sample, laxaphycins A and B4, were shown to act synergistically to inhibit the growth of HCT116 colorectal cancer cells.
- Cai, Weijing,Matthew, Susan,Chen, Qi-Yin,Paul, Valerie J.,Luesch, Hendrik
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p. 2310 - 2319
(2018/04/02)
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- D - [...] manufacturing method
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Provided is a method for producing D-alloisoleucine in a fewer steps and with high yield by an asymmetric transformation reaction of L-isoleucine. A method for producing D-alloisoleucine, involving a step of allowing a tartaric acid derivative represented by general formula (1) (wherein n R's independently represent a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a chlorine atom, a bromine atom or a nitro group; and n represents 0, 1 or 2) to exist in a specific reaction system in which L-isoleucine and D-alloisoleucine can be epimerized to each other, thereby causing a complex of D-alloisoleucine and the tartaric acid derivative to be crystallized.
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Paragraph 0040
(2018/06/12)
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- NMR-based assignment of isoleucine: Vs. allo -isoleucine stereochemistry
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A simple 1H and 13C NMR spectrometric analysis is demonstrated that permits differentiation of isoleucine and allo-isoleucine residues by inspection of the chemical shift and coupling constants of the signals associated with the proton and carbon at the α-stereocentre. This is applied to the estimation of epimerisation during metal-free N-arylation and peptide coupling reactions.
- Anderson, Zoe J.,Hobson, Christian,Needley, Rebecca,Song, Lijiang,Perryman, Michael S.,Kerby, Paul,Fox, David J.
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supporting information
p. 9372 - 9378
(2017/11/22)
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- Jamaicensamide A, a Peptide Containing β-Amino-α-keto and Thiazole-Homologated η-Amino Acid Residues from the Sponge Plakina jamaicensis
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A new cyclic peptide, jamaicensamide A, composed of six amino acids, including a thiazole-homologated amino acid, was isolated from the Bahamian sponge Plakina jamaicensis, along with known compounds bitungolide A and franklinolide A. The structure of the title peptide was solved by integrated analysis of MS, 1D and 2D NMR data, oxidation-hydrolyses to α-amino acids, and their stereodetermination by Marfey's method. The close structural resemblance of Western Atlantic-derived jamaicensamide A to known Western Pacific-derived peptides of lithistid sponges in the genus Theonella and Discodermia suggests a common origin: the symbiotic bacterium Entotheonella sp., a so-called "talented producer" responsible for biosynthesis of most Theonella-associated peptides. Similar natural products from sponges of disparate genera evince the likelihood that these invertebrates harbor the same or a very similar symbiont.
- Jamison, Matthew T.,Molinski, Tadeusz F.
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supporting information
p. 2243 - 2249
(2016/10/04)
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- Vanadium(V)-catalyzed epimerization of isoleucine
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All stereoisomers of isoleucine were transformed to the mixtures of the corresponding epimers by epimerization in alkaline aqueous solution. The catalyst was formed in situ by condensation of salicylaldehyde and isoleucine followed by complexation with va
- Krivosudsky, Luká?,Schwendt, Peter,Filo, Juraj
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- Versiquinazolines A-K, Fumiquinazoline-Type Alkaloids from the Gorgonian-Derived Fungus Aspergillus versicolor LZD-14-1
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Eleven fumiquinazoline-type alkaloids, namely, versiquinazolines A-K (1-11), along with cottoquinazolines B-D, were isolated from the gorgonian-derived fungus Aspergillus versicolor LZD-14-1. Their structures were determined by extensive analyses of the spectroscopic data (1D and 2D NMR, HRESIMS), in addition to the experimental and calculated ECD data and X-ray single-crystal diffraction analysis for the assignments of the absolute configurations. Versiquinazolines A, B, and F (1, 2, and 6), bearing a methanediamine or an aminomethanol unit and representing a unique subtype of fumiquinazolines, were found from nature for the first time. Possible biogenetic relationships of the versiquinazolines are postulated. In addition, the structures of cottoquinazolines B (12), D (13), and C (14) should be revised to the enantiomers. Compounds 1, 2, 7, and 11 exhibited inhibitory activities against thioredoxin reductase (IC50 values ranging from 12 to 20 μM).
- Cheng, Zhongbin,Lou, Lanlan,Liu, Dong,Li, Xiaodan,Proksch, Peter,Yin, Sheng,Lin, Wenhan
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p. 2941 - 2952
(2016/12/07)
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- SEPARATING AGENT AND MANUFACTURING METHOD THEREOF
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An embodiment of the present invention is a separating agent wherein a group represented by a chemical formula of: or a group represented by a chemical formula of: is introduced on a surface thereof.
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Paragraph 0067; 0068; 0069; 0070; 0071; 0072; 0081; 0082
(2015/01/07)
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- Maedamide, a novel chymotrypsin inhibitor from a marine cyanobacterial assemblage of Lyngbya sp.
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Maedamide, a novel chymotrypsin-inhibiting depsipeptide, was isolated from a cyanobacterial assemblage that mostly consisted of Lyngbya sp. Its structure was elucidated by spectroscopic analyses and chiral HPLC analyses of hydrolysis products. Maedamide selectively inhibited chymotrypsin but not elastase and trypsin. In addition, Maedamide strongly inhibited the growth of HeLa cells and HL60 cells.
- Iwasaki, Arihiro,Ohno, Osamu,Sumimoto, Shinpei,Suda, Shoichiro,Suenaga, Kiyotake
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supporting information
p. 4126 - 4128
(2015/02/19)
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- Maedamide, a novel chymotrypsin inhibitor from a marine cyanobacterial assemblage of Lyngbya sp.
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Maedamide, a novel chymotrypsin-inhibiting depsipeptide, was isolated from a cyanobacterial assemblage that mostly consisted of Lyngbya sp. Its structure was elucidated by spectroscopic analyses and chiral HPLC analyses of hydrolysis products. Maedamide selectively inhibited chymotrypsin but not elastase and trypsin. In addition, Maedamide strongly inhibited the growth of HeLa cells and HL60 cells.
- Iwasaki, Arihiro,Ohno, Osamu,Sumimoto, Shinpei,Suda, Shoichiro,Suenaga, Kiyotake
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supporting information
p. 4126 - 4128
(2014/07/22)
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- Balgacyclamides, antiplasmodial heterocyclic peptides from Microcystis aeruguinosa EAWAG 251
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The isolation and structural characterization of three new heterocyclic and macrocyclic peptides, balgacyclamides A-C, from Microcystis aeruginosa EAWAG 251 are reported. The constitutions were determined by 2D-NMR methods and mass spectrometry, and the configurations were assigned after ozonolysis and hydrolysis by HPLC-MS methods using Marfey's method as well as GC-MS using authentic standards. Balgacyclamides A and B were active against Plasmodium falciparum K1 in the low micromolar range, while displaying low toxicity to rat myoblasts.
- Portmann, Cyril,Sieber, Simon,Wirthensohn, Silvan,Blom, Judith F.,Da Silva, Laeticia,Baudat, Emilie,Kaiser, Marcel,Brun, Reto,Gademann, Karl
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p. 557 - 562
(2014/04/17)
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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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- Asperterrestide A, a cytotoxic cyclic tetrapeptide from the marine-derived fungus Aspergillus terreus SCSGAF0162
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A new cytotoxic and antiviral cyclic tetrapeptide, asperterrestide A (1), a new alkaloid, terremide C (2), and a new aromatic butenolide, aspernolide E (3), together with 10 known compounds were isolated from the fermentation broth of the marine-derived fungus Aspergillus terreus SCSGAF0162. Their structures were elucidated by spectroscopic analysis, and the absolute configuration of 1 was determined by the Mosher ester technique and analysis of the acid hydrolysates using a chiral-phase HPLC column. Compound 1 contains a rare 3-OH-N-CH3-Phe residue and showed cytotoxicity against U937 and MOLT4 human carcinoma cell lines and inhibitory effects on influenza virus strains H1N1 and H3N2.
- He, Fei,Bao, Jie,Zhang, Xiao-Yong,Tu, Zheng-Chao,Shi, Yi-Ming,Qi, Shu-Hua
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supporting information
p. 1182 - 1186
(2013/07/26)
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- Champacyclin, a new cyclic octapeptide from Streptomyces strain C42 isolated from the Baltic Sea
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New isolates of Streptomyces champavatii were isolated from marine sediments of the Gotland Deep (Baltic Sea), from the Urania Basin (Eastern Mediterranean), and from the Kiel Bight (Baltic Sea). The isolates produced several oligopeptidic secondary metabolites, including the new octapeptide champacyclin (1a) present in all three strains. Herein, we report on the isolation, structure elucidation and determination of the absolute stereochemistry of this isoleucine/leucine (Ile/Leu = Xle) rich cyclic octapeptide champacyclin (1a). As 2D nuclear magnetic resonance (NMR) spectroscopy could not fully resolve the structure of (1a), additional information on sequence and configuration of stereocenters were obtained by a combination of multi stage mass spectrometry (MSn) studies, amino acid analysis, partial hydrolysis and subsequent enantiomer analytics with gas chromatography positive chmical ionization/electron impact mass spectrometry (GC-PCI/EI-MS) supported by comparison to reference dipeptides. Proof of the head-to-tail cyclization of (1a) was accomplished by solid phase peptide synthesis (SPPS) compared to an alternatively side chain cyclized derivative (2). Champacyclin (1a) is likely synthesized by a non-ribosomal peptide synthetase (NRPS), because of high content of (D)-amino acids. The compound (1a) showed antimicrobial activity against the phytopathogen Erwinia amylovora causing the fire blight disease of certain plants.
- Pesic, Alexander,Baumann, Heike I.,Kleinschmidt, Katrin,Ensle, Paul,Wiese, Jutta,Suessmuth, Roderich D.,Imhoff, Johannes F.
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p. 4834 - 4857
(2014/02/14)
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- Bromine-and chlorine-containing aeruginosins from microcystis aeruginosa bloom material collected in Kibbutz Geva, Israel
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Five new natural products, aeruginosins GE686 (1), GE766 (2), GE730 (3), GE810 (4), and GE642 (5), were isolated along with four known aeruginosins, 98C, 101, KY642, and DA688, from bloom material of the cyanobacterium Microcystis aeruginosa collected from a fish pond in Kibbutz Geva, Israel, in August 2007. Their structures were elucidated by a combination of various spectroscopic techniques, primarily NMR and MS, while the absolute configurations of the stereogenic centers were determined by Marfey's and chiral-phase HPLC methods. Two of the new aeruginosins, aeruginosins GE686 (1) and GE766 (2), contain the unprecedented d-m-Br-m′-Cl-p-hydroxyphenyllactic acid derivative. The structures and biological activities of the five new metabolites are described.
- Elkobi-Peer, Shira,Faigenbaum, Raya,Carmeli, Shmuel
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p. 2144 - 2151
(2013/02/25)
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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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- Stereoselective incorporation of isoleucine into cypridina luciferin in Cypridina hilgendorfii (Vargula hilgendorfii)
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The emission of light in the marine ostracod Cypridina hilgendorfii (presently Vargula hilgendorfii) is produced by the Cypridina luciferin-luciferase reaction in the presence of molecular oxygen. Cypridina luciferin has an asymmetric carbon derived from isoleucine, and the absolute configuration is identical to the C-3 position in L-isoleucine or D-alloisoleucine. To determine the stereoselective incorporation of the isoleucine isomers (L-isoleucine, D-isoleucine, L-alloisoleucine, and D-alloisoleucine), we synthesized four 2H-labeled isoleucine isomers and examined their incorporation into Cypridina luciferin by feeding experiments. Judging by these results, L-isoleucine is predominantly incorporated into Cypridina luciferin. This suggests that the isoleucine unit of Cypridina luciferin is derived from L-isoleucine, but not from D-alloisoleucine.
- Kato, Shin-Ichi,Oba, Yuichi,Ojika, Makoto,Inouye, Satoshi
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p. 1528 - 1532
(2008/02/13)
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- Creation of a broad-range and highly stereoselective D-amino acid dehydrogenase for the one-step synthesis of D-amino acids
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Using both rational and random mutagenesis, we have created the first known broad substrate range, nicotinamide cofactor dependent, and highly stereoselective D-amino acid dehydrogenase. This new enzyme is capable of producing D-amino acids via the reductive amination of the corresponding 2-keto acid with ammonia. This biocatalyst was the result of three rounds of mutagenesis and screening performed on the enzyme meso-diaminopimelate D-dehydrogenase. The first round targeted the active site of the wild-type enzyme and produced mutants that were no longer strictly dependent on the native substrate. The second and third rounds produced mutants that had an increased substrate range including straight-and branched-aliphatic amino acids and aromatic amino acids. The very high selectivity toward the D-enantiomer (95 to >99% ee) was shown to be preserved even after the addition of the five mutations found in the three rounds of mutagenesis and screening. This new enzyme could complement and improve upon current methods for D-amino acid synthesis.
- Vedha-Peters, Kavitha,Gunawardana, Manjula,Rozzell, J. David,Novick, Scott J.
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p. 10923 - 10929
(2007/10/03)
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- Antimicrobial metabolites produced by an intertidal Acremonium furcatum
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In a screening for antimicrobial metabolites, amides of d-allo- and l-isoleucine derivatives were isolated from the culture of a marine strain of Acremonium furcatum. Structural elucidation of these compounds was performed by analysis of spectroscopic data and confirmed by synthesis. All of the compounds, natural and synthetic intermediates, were bioassayed against bacteria and phytopathogenic fungi, with many showing remarkable antifungal activities.
- Gallardo, Gabriela L.,Butler, Matias,Gallo, Mariana L.,Rodriguez, M. Alejandra,Eberlin, Marcos N.,Cabrera, Gabriela M.
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p. 2403 - 2410
(2007/10/03)
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- Determination of the complete absolute configuration of petriellin A
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We report the full structural determination of the depsipeptide petriellin A. The absolute configuration of the amino acid residues, N-methyl isoleucine and N-methyl threonine, have been determined by a combination of HPLC and TLC comparison of synthetic Marfey's derivatives and Marfey's derivatives of the natural product hydrolysate. The configuration of the chiral centres in these two N-methylated residues was found to be the same as those of the common unmethylated l-amino acids. CSIRO 2006.
- Aurelio, Luigi,Brownlee, Robert T. C.,Dang, Jason,Hughes, Andrew B.,Polya, Gideon M.
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p. 407 - 414
(2008/02/04)
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- Direct synthesis of unprotected α-amino acids via allylation of hydroxyglycine
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Hydroxyglycine, the ammonia adduct of glyoxylic acid, was found to react with various allylboronates in the presence of triethylamine in methanol to give unprotected α-amino acids directly with high stereoselectivity. For instance, the reactions with (E)- and (Z)-crotylboronates afforded the corresponding anti- and syn-crotylated products (isoleucine and alloisoleucine after hydrogenation) with high diastereoselectivity, respectively. Interestingly, it was found that isomerization of the products (γ-adducts to α-adducts) occurred under the reaction conditions in some cases. Control experiments have suggested that the isomerization took place via 2-aza (or azonia) Cope rearrangement of imines derived from γ-adducts and glyoxylic acid.
- Sugiura, Masaharu,Mori, Chieko,Hirano, Keiichi,Kobayashi, Shu
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p. 937 - 942
(2007/10/03)
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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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- 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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- 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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- Stereospecific, enantioselective allylation of α-hydrazono esters by using allyltrichlorosilanes with BINAP dioxides as neutral-coordinate organocatalysts
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(Chemical equation presented). Excellent diastereo- and enantioselectivities were obtained in the title reaction, (E)-Crotylsilanes gave syn adducts, whereas anti adducts were obtained from (Z)-crotylsilanes (see scheme).
- Ogawa, Chikako,Sugiura, Masaharu,Kobayashi, Shu
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p. 6491 - 6493
(2007/10/03)
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- Chemo-enzymatic approach to D-allo-isoleucine
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A mixture of D-alloisoleucine and L-isoleucine derivatives are selectively hydrolysed by enzymatic catalysis (alcalase) allowing the recovery of the D-allo stereoisomer in excellent d.e. and yields. Thus, N-formyl-D-allo- isoleucine benzylester is obtained after enzymatic hydrolysis of the diastereoisomeric mixture or by a crystallisation procedure.
- Cambie, Mara,D'Arrigo, Paola,Fasoli, Ezio,Servi, Stefano,Tessaro, Davide,Canevotti, Francesco,Del Corona, Lucio
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p. 3189 - 3196
(2007/10/03)
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- Method for producing D-allo -isoleucine
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A method for producing D-allo-isoleucine is provided. The method comprises converting L-isoleucine to the corresponding hydantoin. Amixture containing the hydantoin is contacted with a D-hydantoinase to stereoselectively hydrolyze any D-allo-isoleucine hydantoin in the mixture to the corresponding N-carbamoyl-D-allo-isoleucine. The N-carbamoyl-D-allo-isoleucine is decarbamoylated to produce D-allo-isoleucine. Preferably the contacting of the hydantoin with a D-hydantoinase is carried out under conditions permitting the simultaneous epimerization of the chiral center at C-5 of the hydantoin.
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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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- 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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- 20(S) camptothecin glycoconjugates
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The present invention relates to glycoconjugates of 20(S)-camptothecin, in which a 3-O-methylated β-L-fucose unit is linked to the 20-hydroxyl group of a camptothecin derivative via a thiourea-modified peptide spacer. The invention furthermore relates to processes for the preparation of the compounds according to the invention and to their use as medicaments, in particular in connection with oncoses.
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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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- Monoclonal antibody against human telomerase catalytic subunit
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The present invention provides a monoclonal antibody which can specifically and efficiently recognize hTERT protein; which is the catalytic subunit of telomerase, and provides a human chimeric antibody, a CDR grafted antibody, a single chain antibody, and a disulfide stabilized antibody each containing the monoclonal antibody. In addition, the present invention provides a method for detecting/quantitating hTERT protein using these antibodies, and provides diagnosis method, diagnosis agent, and therapeutic agent, for diseases, such as cancer, in which telomerase is involved using these bodies.
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- Human CDR-grafted antibody and antibody fragment thereof
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A human CDR-grafted antibody or the antibody fragment thereof which specifically reacts with the extracellular region of human CC chemokine receptor 4 (CCR4) but does not react with a human blood platelet; a human CDR-grafted antibody or the antibody fragment thereof which specifically reacts with the extracellular region of CCR4 and has a cytotoxic activity against a CCR4-expressing cell; and a medicament, a therapeutic agent or a diagnostic agent comprising at least one of the antibodies and the antibody fragments thereof as an active ingredient.
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- N1 modified glycopeptides
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Described herein are N′-acylated derivatives of desleucylA82846B. The compounds are useful as antibacterial agents.
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- Stereoinversion of β- and γ-substituted α-amino acids using a chemo-enzymatic oxidation-reduction procedure
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Both D- and L-β- and γ-substituted α-amino acids can be interconverted to their respective L- and D- diastereoisomers by treatment with an enantioselective amino acid oxidase and a chemical reducing agent.
- Enright, Alexis,Alexandre, Francois-Rene,Roff, Geoffrey,Fotheringham, Ian G.,Dawson, Michael J.,Turner, Nicholas J.
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p. 2636 - 2637
(2007/10/03)
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- Total synthesis of the amino hip analogue of didemnin A
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Disclosed is a synthetic method for the preparation of analogs of Didemnin A (1), particularly the Amino-Hip analog of Didemnin A, also known as “AipDidemnin A” (8). These compounds have the following structures:
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- Gene recombinant antibody and antibody fragment thereof
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A recombinant antibody or the antibody fragment thereof which specifically reacts with an extracellular domain of human CCR4; a DNA which encodes the recombinant antibody or the antibody fragment thereof; a method for producing the recombinant antibody or the antibody fragment thereof; a method for immunologically detecting CCR4, a method for immunologically detecting a cell which expressed CCR4 on the cell surface, a method for depleting a cell which expresses CCR4 on the cell surface, and a method for inhibiting production of Th2 cytokine, which comprise using the recombinant antibody according or antibody fragment thereof; a therapeutic or diagnostic agent for Th2-mediated immune diseases; and a therapeutic or diagnostic agent for a blood cancer.
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- Solvent systems for pharmaceutical agents
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The invention provides compositions, solvent systems, and methods for solubilizing compounds which are otherwise difficult to solubilize. The invention involves the use of a structured fluid (e.g. a liquid crystalline phase, an L1 phase, an L2 phase, an L3 phase, an emulsion, or a microemulsion), comprising a polar solvent, a lipid or a surfactant, and an essential oil or a dissolution/solubilization agent.
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- DNA encoding the human synapsin III gene and uses thereof
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A new synapsin protein, designated synapsin III, its amino acid sequence, and its human gene have been isolated and characterized. Furthermore, isoforms of synapsin III, e.g., synapsin IIIa, IIIb and IIIc, and have isolated and characterized, and cDNA encoding these isoforms has also been isolated and characterized. The synapsin III gene is located on human chromosome 22, in the vicinity of a region previously identified as a susceptibility locus for schizophrenia. The information and experimental tools provided by this discovery can be used to generate new therapeutic agents or diagnostic assays for this new protein, its associated mRNA or its associated genomic DNA. Due to its role in neurotransmission and synaptogenesis, isoforms of synapsin III are associated with the symptoms of psychiatric diseases, especially schizophrenia.
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- Inhibition of HIV-1 replication using d-amino acid peptides
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The Tat-inhibitory polypeptide derivatives of the formula I D-Cys-D-Phe-D-Thr-D-Thr-D-Lys-D-Ala-D-Leu-D-Gly-D-Ile-D-Ser-D-Tyr-D-Gly-D-Arg-D-Lys-D-Lys-D-Arg-D-Arg-D-Gln-D-Arg-D-Arg-D-Arg-D-Pro-D-Pro-D-Gln-D-Gly-D-Ser-D-Gln-D-Thr-D-His-D-Gln-D-Val-D-Ser-D-Leu-D-Ser-D-Lys-D-Gln (SEQ ID 1) and fragments or analogs thereof, and the biologically and pharmaceutically acceptable salts thereof exhibit advantageous properties, including binding to ΔTAR, inhibition of LTR-dependent reporter gene expression in a model cell assay and, finally, inhibition of HIV-1 replication, as determined in assays of HIV-induced syncytium formation, cytotoxicity and reverse transcriptase production. These peptides are thus capable of competing with the TAR RNA-binding domain of Tat protein and thus are useful as a therapeutic agents in the treatment of AIDS.
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- T-cell selective interleukin-4 agonists
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This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of interleukin 4. Further, the invention is directed to IL-4 muteins having single and double mutations represented by the designators R121E and T13D/R121E, 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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- Method of using PON-1 to decrease atheroma formation
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The invention is directed to a method of decreasing atheroma formation in a mammal comprising administering a pharmaceutically effective amount of PON-1 or its functional equivalent to a patient in need thereof. Also included herein are pharmaceutical compositions, and a method for diagnosing predisposition to hypercholesterolemia by assessing the level of native circulating PON-1.
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- ASSAYS FOR HOMOCYSTEINE AND HOMOCYSTEINE DESULPHURASE FROM PROTOZOAN TRICHOMONASVAGINALIS
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The present invention relates to an assay for determining homocysteine, cysteine, O-acetyl-L-serine and/or methionine levels in a biological sample using an enzyme that catalyzes the degradation of homocysteine, cysteine, O-acetyl-L-serine and methionine. The enzyme being more particularly homocysteine desulphurase, a polynucleotide fragment encoding protozoan homocysteine desulphurase, a recombinant vector comprising a polynucleotide fragment, transformed cells, the protozoan homocysteine desulphurase polypeptide, and pharmaceutical compositions comprising recombinant homocysteine desulphurase for use in medicine or veterinary medicine.
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