- Vanadium(V)-catalyzed epimerization of isoleucine
-
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
-
-
Read Online
- Action of L-aminoacylase and L-amino acid oxidase on 2-amino-3- methylpent-4-enoic acid [Δ(4)-dehydroisoleucine and alloisoleucine] stereoisomers: An alternative route to a stereochemically pure compound and the application to the synthesis of (R)-2-methylbutan-1-ol
-
The action of L-aminoacylase and L-amino acid oxidase on the stereoisomers of 2-amino-3-methylpent-4-enoic acid was examined, to secure stereochemically pure compounds related to L-alloisoleucine. A scalemic mixture [(2S,3R)- (90.0%), (2S,3S)(3.2%), (2R,3S)- (5.9%), (2R,3R)- (0.9%)] of the N-trifluoroacetyl derivatives of the title compound, which was prepared by an asymmetric Claisen rearrangement, was submitted to Aspergillus L-aminoacylase-catalyzed hydrolysis. Only the (2S,3R)- and (2S,3S)isomers were hydrolyzed to give the corresponding amino acids. The subsequent treatment of these isomers with Crotalus adamanteus L-amino acid oxidase afforded the pure (2S,3R)-isomer, related to L-alloisoleucine, in more than 99% stereochemically pure form. Moreover, the product was converted to L- alloisoleucine and (R)-2-methylbutan-1-ol via a chemoenzymatic procedure.
- Bakke, Mikio,Ohta, Hiromichi,Kazmaier, Uli,Sugai, Takeshi
-
-
Read Online
- Versiquinazolines A-K, Fumiquinazoline-Type Alkaloids from the Gorgonian-Derived Fungus Aspergillus versicolor LZD-14-1
-
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
-
-
Read Online
- OPTICAL RESOLUTION OF DL-VALINE, DL-LEUCINE, AND DL-ISOLEUCINE BY FORMATION OF ADDUCT WITH L-PHENYLALANINE.
-
An alkaline solution containing L-phenylalanine (L-Phe) and one of DL-leucine, and DL-isoleucine is allowed to selectively form a precipitate composed of L-Phe and the aliphatic D-amino acid by adjusting the pH of initial solution to around 5. 5 with hydrochloric acid **1H NMR spectra in deuterium oxide, elemental analyses, and infrared spectra of the precipitates indicate that they are adducts of the aliphatic D-amino acid and L-Phe in the molar ratio of 1:1. The free aliphatic D-amino acids with high optical purity (84-100%) may be recovered fromthe adducts in 49-63% yield. An attempt was made to obtain both the aliphatic D- and L-amino acids by using an aqueous solution containing the aliphatic DL-amino acid and L-Phe as an initial solution.
- Shiraiwa,Ikawa,Sakaguchi,Kurokawa
-
-
Read Online
- Deciphering the Biosynthetic Origin of L-allo-Isoleucine
-
The nonproteinogenic amino acid l-allo-isoleucine (l-allo-Ile) is featured in an assortment of life forms comprised of, but not limited to, bacteria, fungi, plants and mammalian systems including Homo sapiens. Despite its ubiquity and functional importance, the specific origins of this unique amino acid have eluded characterization. In this study, we describe the discovery and characterization of two enzyme pairs consisting of a pyridoxal 5′-phosphate (PLP)-linked aminotransferase and an unprecedented isomerase synergistically responsible for the biosynthesis of l-allo-Ile from l-isoleucine (l-Ile) in natural products. DsaD/DsaE from the desotamide biosynthetic pathway in Streptomyces scopuliridis SCSIO ZJ46, and MfnO/MfnH from the marformycin biosynthetic pathway in Streptomyces drozdowiczii SCSIO 10141 drive l-allo-Ile generation in each respective system. In vivo gene inactivations validated the importance of the DsaD/DsaE pair and MfnO/MfnH pair in l-allo-Ile unit biosynthesis. Inactivation of PLP-linked aminotransferases DsaD and MfnO led to significantly diminished desotamide and marformycin titers, respectively. Additionally, inactivation of the isomerase genes dsaE and mfnH completely abolished production of all l-allo-Ile-containing metabolites in both biosynthetic pathways. Notably, in vitro biochemical assays revealed that DsaD/DsaE and MfnO/MfnH each catalyze a bidirectional reaction between l-allo-Ile and l-Ile. Site-directed mutagenesis experiments revealed that the enzymatic reaction involves a PLP-linked ketimine intermediate and uses an arginine residue from the C-terminus of each isomerase to epimerize the amino acid β-position. Consequently, these data provide important new insight into the origins of l-allo-Ile in natural products with medicinal potential and illuminate new possibilities for biotool development.
- Li, Qinglian,Qin, Xiangjing,Liu, Jing,Gui, Chun,Wang, Bo,Li, Jie,Ju, Jianhua
-
-
Read Online
- Practical synthesis of (+)-alloisoleucine
-
Subsequent treatment of N-crotoyl-(1S,2R)-bornane-10,2-sultam with EtMgCl, recrystallization of the product and saponification, afforded R-(-)- 3-methylpenthanoic acid which was used for acylation of (1R,2S)-bornane-10,2- sultam. The product was converted into N-[(2S,3R)-2-amino-3- methylpentanoyl](1R,2S)-bornane-10,2-sultam by hydroxyamination with 1- chloro-1-nitrosocyclohexane, followed by reduction of the hydroxylamine grouping. Saponification of the sultam imide provided (+)-alloisoleucine.
- Belzecki, Czeslaw,Trojnar, Jerzy,Chmielewski, Marek
-
-
Read Online
- Structural relationships in crystals accommodating different stereoisomers of 2-amino-3-methylpentanoic acid
-
A reinvestigation of the crystal structure of the 1:1 mixture of the two racemates DL-isoleucine and DL-allo-isoleucine, with a detailed analysis of interatomic distances between alternative side-chain positions, reveals a systematic distribution of the four stereoisomers in this crystal. Two different molecular chains exist in the crystal and each such chain accommodates a single diastereomeric pair only (L-isoleucine:D-allo-isoleucine or D-isoleucine:L-allo-isoleucine). The crystal is built up by a stacking of such chains in two dimensions and three different packing modes for the two types of chains are discussed. Crystallization experiments of the two individual racemates in the 1:1 mixture of DL-isoleucine:DL-allo-isoleucine have been undertaken. The structure of the racemate DL-isoleucine is presented. The molecular arrangements in this racemate and the 1:1 DL-isoleucine:DL-allo-isoleucine mixture are closely related. Furthermore, the spontaneous resolution of enantiomers upon crystallization of the other racemate, DL-allo-isoleucine, is rationalized on the basis of the aforementioned analysis of interatomic distances in the 1:1 DL-isoleucine:DL-allo-isoleucine complex. Structural data for a new L-isoleucine: D-allo-isoleucine complex are also given.
- Dalhus, Bjoorn,Goerbitz, Carl Henrik
-
-
Read Online
- Lagunamides A and B: Cytotoxic and antimalarial cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula
-
Lagunamides A (1) and B (2) are new cyclic depsipeptides isolated from the marine cyanobacterium Lyngbya majuscula obtained from Pulau Hantu Besar, Singapore. The planar structural characterization of these molecules was achieved by extensive spectroscopic analysis, including 2D NMR experiments. In addition to Marfey's method and 3JH-H coupling constant values, a modified method based on Mosher's reagents and analysis using LC-MS was deployed for the determination of the absolute configuration. Lagunamides A and B displayed significant antimalarial properties, with IC50 values of 0.19 and 0.91 μM, respectively, when tested against Plasmodium falciparum. Lagunamides A and B also possessed potent cytotoxic activity against P388 murine leukemia cell lines, with IC50 values of 6.4 and 20.5 nM, respectively. Furthermore, these cyanobacterial compounds exhibited moderate antiswarming activities when tested against Pseudomonas aeruginosa PA01.
- Tripathi, Ashootosh,Puddick, Jonathan,Prinsep, Michele R.,Rottmann, Matthias,Tan, Lik Tong
-
-
Read Online
- Jamaicensamide A, a Peptide Containing β-Amino-α-keto and Thiazole-Homologated η-Amino Acid Residues from the Sponge Plakina jamaicensis
-
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.
-
-
Read Online
- METHODS AND MATERIALS FOR ASSESSING AND TREATING OBESITY
-
This document relates to methods and materials for assessing and/or treating obese mammals (e.g., obese humans). For example, methods and materials for using one or more interventions (e.g., one or more pharmacological interventions) to treat obesity and/or obesity-related comorbidities in a mammal (e.g., a human) identified as being likely to respond to a particular intervention (e.g., a pharmacological intervention) are provided.
- -
-
-
- 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)
-
- Asymmetric β-Methylation of l- and d-α-Amino Acids by a Self-Contained Enzyme Cascade
-
This report describes a modular enzyme-catalyzed cascade reaction that transforms l- or d-α-amino acids to β-methyl-α-amino acids. In this process an α-amino acid transaminase, an α-keto acid methyltransferase, and a halide methyltransferase cooperate in two orthogonal reaction cycles that mediate product formation and regeneration of the cofactor pyridoxal-5′-phosphate and the co-substrate S-adenosylmethionine. The only stoichiometric reagents consumed in this process are the unprotected l- or d-α-amino acid and methyl iodide.
- Liao, Cangsong,Seebeck, Florian P.
-
supporting information
p. 7184 - 7187
(2020/03/17)
-
- 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)
-
- Resolution of α/β-amino acids by enantioselective penicillin G acylase from Achromobacter sp.
-
Penicillin G acylases (PGAs) are enantioselective enzymes catalyzing a hydrolysis of stable amide bond in a broad spectrum of substrates. Among them, derivatives of α- and β-amino acids represent a class of compounds with high application potential. PGAEc from Escherichia coli and PGAA from Achromobacter sp. CCM 4824 were used to catalyze enantioselective hydrolyses of seven selected N-phenylacetylated α/β-amino acid racemates. The PGAA showed higher stereoselectivity for enantiomers of N-PhAc-β-homoleucine, N-PhAc-α-tert-leucine and N-PhAc-β-leucine. To study the mechanism of enantiodiscrimination on molecular level, we have constructed a homology model of PGAA that was used in molecular docking experiments with the same substrates. In-silico experiments successfully reproduced the data from experimental enzymatic resolutions confirming validity of employed modeling protocol. We employed this protocol to evaluate enantiopreference of PGAA towards seven new substrates with application potential. For five of them, high enantioselectivity of PGAA was predicted.
- Grulich, Michal,Brezovsky, Jan,?těpánek, Václav,Palyzová, Andrea,Kyslíková, Eva,Kyslík, Pavel
-
p. 240 - 247
(2015/10/28)
-
- SEPARATING AGENT AND MANUFACTURING METHOD THEREOF
-
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.
- -
-
Paragraph 0067; 0068; 0069; 0070; 0071; 0072; 0081; 0082
(2015/01/07)
-
- Asperterrestide A, a cytotoxic cyclic tetrapeptide from the marine-derived fungus Aspergillus terreus SCSGAF0162
-
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
-
supporting information
p. 1182 - 1186
(2013/07/26)
-
- Biocatalytic asymmetric synthesis of unnatural amino acids through the cascade transfer of amino groups from primary amines onto keto acids
-
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
-
p. 3538 - 3542
(2014/01/06)
-
- Cyclic heptapeptides, cordyheptapeptides C-E, from the marine-derived fungus Acremonium persicinum SCSIO 115 and their cytotoxic activities
-
Three new cycloheptapeptides, cordyheptapeptides C-E (1-3), were isolated from the fermentation extract of the marine-derived fungus Acremonium persicinum SCSIO 115. Their planar structures were elucidated on the basis of extensive MS, as well as 1D and 2
- Chen, Ziming,Song, Yongxiang,Chen, Yuchan,Huang, Hongbo,Zhang, Weimin,Ju, Jianhua
-
p. 1215 - 1219
(2012/11/13)
-
- Lagunamide C, a cytotoxic cyclodepsipeptide from the marine cyanobacterium Lyngbya majuscula
-
Lagunamide C (1) is a cytotoxic cyclodepsipeptide isolated from the marine cyanobacterium, Lyngbya majuscula, from the western lagoon of Pulau Hantu Besar, Singapore. The complete structural characterization of the molecule was achieved by extensive NMR spectroscopic analysis as well as chemical manipulations. Several methods, including the advanced Marfey's method, a modified method based on derivatization with Mosher's reagents and analysis using LC-MS, and the use of 3JH-H coupling constant values, were utilized for the determination of its absolute configuration. Compound 1 is related to the aurilide-class of molecules and it differs mainly in the macrocyclic structure by having a 27 membered ring system due to additional methylene carbon in the polyketide moiety. Lagunamide C displayed potent cytotoxic activity against a panel of cancer cell lines, such as P388, A549, PC3, HCT8, and SK-OV3 cell lines, with IC50 values ranging from 2.1 nM to 24.4 nM. Compound 1 also displayed significant antimalarial activity with IC50 value of 0.29 μM when tested against Plasmodium falciparum. In addition, lagunamide C exhibited weak anti-swarming activity when tested at 100 ppm against the Gram-negative bacterial strain, Pseudomonas aeruginosa PA01.
- Tripathi, Ashootosh,Puddick, Jonathan,Prinsep, Michele R.,Rottmann, Matthias,Chan, Kok Ping,Chen, David Yu-Kai,Tan, Lik Tong
-
experimental part
p. 2369 - 2375
(2012/02/03)
-
- Cyclopeptide alkaloids of Zizyphus xylopyra
-
14-Membered cyclopeptide alkaloids, franganine, frangufoline, amphibine-D and mauritine-A has been isolated from the whole plant of Zizyphus xylopyra and their structures established by spectral evidences. This is the first report of these alkaloids from Z. xylopyra.
- Rai, Nisha,Singh, Sarita,Singh,Pandey
-
experimental part
p. 336 - 337
(2009/06/25)
-
- Compositions, kits, and methods relating to the human FEZ1 gene, a novel tumor suppressor gene
-
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.
- -
-
-
- Stereoselective incorporation of isoleucine into cypridina luciferin in Cypridina hilgendorfii (Vargula hilgendorfii)
-
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
-
p. 1528 - 1532
(2008/02/13)
-
- Determination of the complete absolute configuration of petriellin A
-
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.
-
p. 407 - 414
(2008/02/04)
-
- Direct synthesis of unprotected α-amino acids via allylation of hydroxyglycine
-
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
-
p. 937 - 942
(2007/10/03)
-
- T-CELL SELECTIVE INTERLEUKIN-4 AGONISTS
-
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.
- -
-
-
- CONJUGATES OF TRANSPORTER PEPTIDES AND NUCLEIC ACID ANALOGS, AND THEIR USE
-
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).
- -
-
-
- Protein interaction method and composition
-
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.
- -
-
-
- 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
-
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
-
p. 3020 - 3021
(2007/10/03)
-
- Method for producing D-allo -isoleucine
-
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.
- -
-
-
- Inhibition of BEHAB cleavage and primary central nervous system (CNS) tumors
-
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.
- -
-
-
- Compositions, methods, and kits relating to resistin-like molecules
-
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.
- -
-
-
- Carbohydrate epitope mimic compounds and uses thereof
-
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.
- -
-
-
- 20(S) camptothecin glycoconjugates
-
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.
- -
-
-
- Mammalian prestin polynucleotides
-
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.
- -
-
-
- Monoclonal antibody against human telomerase catalytic subunit
-
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.
- -
-
-
- Human CDR-grafted antibody and antibody fragment thereof
-
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.
- -
-
-
- N1 modified glycopeptides
-
Described herein are N′-acylated derivatives of desleucylA82846B. The compounds are useful as antibacterial agents.
- -
-
-
- Total synthesis of the amino hip analogue of didemnin A
-
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:
- -
-
-
- Gene recombinant antibody and antibody fragment thereof
-
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.
- -
-
-
- Solvent systems for pharmaceutical agents
-
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.
- -
-
-
- DNA encoding the human synapsin III gene and uses thereof
-
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.
- -
-
-
- Inhibition of HIV-1 replication using d-amino acid peptides
-
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.
- -
-
-
- T-cell selective interleukin-4 agonists
-
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.
- -
-
-
- Method of using PON-1 to decrease atheroma formation
-
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.
- -
-
-
- ASSAYS FOR HOMOCYSTEINE AND HOMOCYSTEINE DESULPHURASE FROM PROTOZOAN TRICHOMONASVAGINALIS
-
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.
- -
-
-
- Composition of matter having bioactive properties
-
Particles of coordinated complex comprising a basic, hydrous polymer and a capacitance adding compound, as well as methods for their production, are described. These complexes exhibit a high degree of bioactivity making them suitable for a broad range of applications through their incorporation into conventional vehicles benefiting from antimicrobial and similar properties.
- -
-
-
- Telomere repeat binding factors and diagnostic and therapeutic use thereof
-
The present invention relates to a novel nucleotide sequence encoding a telomeric protein which binds a repeat region of telomeric sequences, and to the protein encoded thereby. Also included within the invention are expression vectors for the production of the telomeric protein and host cells transformed with the nucleotide sequence. In addition, antibodies, probes and antagonists specific for the telomeric protein are contemplated. Methods of identifying antagonists of the telomeric protein, diagnostic methods of identifying the telomeric protein in a sample, and therapeutic uses of the telomeric protein, particularly in the treatment of aging and cancer, are also contemplated.
- -
-
-
- Methods of enhancing functioning of the large intestine
-
The invention relates to glucagon-related peptides and their use for the prevention or treatment of disorders involving the large intestine. In particular, it has now been demonstrated that GLP-2 and peptidic agonists of GLP-2 can cause proliferation of the tissue of large intestine. Thus, the invention provides methods of proliferating the large intestine in a subject in need thereof. Further, the methods of the invention are useful to treat or prevent inflammatory conditions of the large intestine, including inflammatory bowel diseases.
- -
-
-
- Bacillus thuringiensis Cry1Ia-Cry1Ba hybrid toxins
-
Bacillus thuringiensishybrid toxin fragment comprising structural domains I, II and III in this order starting from the N-terminal, wherein the domains are derived from at least two different Cry proteins, domain I is domain I of any Bacillus thuringiensisCry protein or a part of said domain or a peptide substantially similar to said domain, domain II is domain II of Cry1la or a part of said domain or a peptide substantially similar to said domain, and domain III is domain III of Cry1Ba or a part of said domain or a peptide substantially similar domain.
- -
-
-
- NOVEL G-PROTEIN COUPLED RECEPTOR PROTEIN AND DNA THEREOF
-
The present invention relates to a human brain-derived protein, a partial peptide thereof or a salt thereof, a DNA encoding the receptor protein, a process for producing the protein, a method for determining a ligand for the protein, a method for screening/a kit for screening a compound which alters property of a ligand binding with the protein, a compound or a salt thereof obtainable by the screening, an antibody to the protein and the like. The human brain-derived protein or the DNA encoding the protein of the present invention are useful as or in 1○ determination of a ligand,2○ obtaining of an antibody and antiserum, 3○ construction of the expression system for a recombinant receptor protein, 4○ development of receptor binding assay using the same expression system and screening of drug candidate compound, 5○ implementation of drug design based on comparison with a ligand receptor having the structural similarity, 6○ reagents for preparing a probe or a PCR primer in gene therapy, 7○ production of a transgenic animal, or 8○ a drug such as an agent for gene prophylaxis or therapy.
- -
-
-
- NOVEL G PROTEIN-CONJUGATED RECEPTOR PROTEIN AND DNA THEREOF
-
The present invention relates to a human brain-derived protein, a partial peptide thereof or a salt thereof, a DNA encoding the receptor protein, a process for producing the protein, a method for determining a ligand for the G protein-coupled receptor protein, a method for screening/a kit for screening a compound which alters property of a ligand binding with the protein, a compound or a salt thereof obtainable by the screening, an antibody to the G protein-coupled receptor protein and the like.The human brain-derived G protein-coupled receptor protein or the DNA encoding the protein of the present invention are useful as or in (1) determination of a ligand, (2) obtaining of an antibody and antiserum, (3) construction of the expression system for a recombinant receptor protein, (4) development of receptor binding assay using the same expression system and screening of drug candidates, (5) implementation of drug design nucleotide on comparison with a ligand receptor having the structural similarity, (6) reagents for preparing a probe or a PCR primer in gene therapy, (7) production of a transgenic animal, or (8) a drug for gene prophylaxis or therapy.
- -
-
-
- Human betacellulin-specific antibodies and uses thereof
-
Disclosed are an antibody which have a binding activity to human betacellulin protein or a mutein thereof with specificity; especially a monoclonal antibody which does not have cross reactitivity with human epidermal growth factor (EGF) and human transforming growth factor a (TGF-α), belongs to the immunoglobulin class of IgG, and,specifically binds to human betacellulin protein to neutralize biological activity thereof; a hybridoma for producing the monoclonal antibody; and a method for producing the monoclonal antibody. Said monoclonal antibody neutralizes biological activity of a human BTC protein, and bind to the protein with high sensitivity and specificity, so that they can be used as a therapeutic agent for diseases such as arterial sclerosis and cancers, and also used as a reagent for assaying the human BTC protein or a mutein thereof and as a diagnostic agent for diabetes or complications thereof.
- -
-
-
- Permucous preparation
-
A composition for permucosal administration characterized by containing Antago-3 or a physiologically acceptable salt thereof, and a sucrose fatty acid ester. With the composition for permucosal administration of the invention there is provided a long-term stable preparation having the high permucosal absorption of physiologically active peptide Antago-3 without irritation.
- -
-
-
- Compositions, kits, and methods for effecting adenine nucleotide modulation of DNA mismatch recognition proteins
-
Compositions, and products comprising a MutS homolog which binds to a mismatched region of a duplex DNA molecule in the presence of ADP are provided, as are methods of binding MutS homologs to mismatched DNA in the presence of ADP. The use of MutL homolog derivatives in combination with MutS homologs is also included. Nonhuman mammals which are nullizygous for both Msh2 and p53 are also provided, as are methods of making and using the same.
- -
-
-
