- 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)
-
- Reconstruction of Hyper-Thermostable Ancestral L-Amino Acid Oxidase to Perform Deracemization to D-Amino Acids
-
L-amino acid oxidases (LAAOs) with broad substrate specificity can be used in the deracemization of D,L-amino acids (D,L-AAs) to their D-enantiomers. Hyper-thermostable LAAO (HTAncLAAO) was designed through a combination of manual sequence data mining and ancestral sequence reconstruction. Soluble expression of HTAncLAAO (>50 mg/L) can be achieved using an E. coli system. HTAncLAAO, which recognizes seven L-AAs as substrates, exhibits extremely high thermal stability and long-term stability; the t1/2 value was 95 °C and 99 % ee, D-enantiomer). These results suggest that HTAncLAAO is an excellent biocatalyst to perform this deracemization.
- Ishida, Chiharu,Miyata, Ryo,Hasebe, Fumihito,Miyata, Azusa,Kumazawa, Shigenori,Ito, Sohei,Nakano, Shogo
-
p. 5228 - 5235
(2021/11/05)
-
- Enantioselective hydrogenation of cyclic tetrasubstituted-olefinic dehydroamino acid derivatives
-
An efficient asymmetric hydrogenation of cyclic tetrasubstituted-olefinic dehydroamino acid derivatives has been achieved with a Rh-ArcPhos catalyst, affording a series of α-acylamino-β-alkyl tetrahydropyranones with two contiguous chiral centers in up to 96% ee and 1000 TON.
- Claverie, Jerome,Tang, Chuyan,Tang, Wenjun,Wan, Feng,Wang, Nan,Zhu, Yuxin
-
p. 5546 - 5549
(2021/06/12)
-
- 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)
-
- Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce
-
Pseudomonas cichorii, which causes varnish spots on lettuce and seriously damages lettuce production during the summer season in the highland areas of Japan (e.g., Nagano and Iwate prefectures) was isolated. The structure of a toxin produced by this organism was analyzed based on the detailed evaluation of its 2D NMR and FABMS spectra, and this compound has not been reported previously. We propose the name cichorinotoxin for this toxin. In conjunction with the D or L configurations of each amino acid, which were determined by Marfey’s method, we propose the structure of cichorinotoxin to be as follows: 3-hydroxydecanoyl-(Z)-dhThr1-D-Pro2-D-Ala3-D-Ala4-D-Ala5-D-Val6-D-Ala7-(Z)-dhThr8-Ala9-Val10-D-Ile11-Ser12-Ala13-Val14-Ala15-Val16-(Z)-dhThr17-D-alloThr18-Ala19-L-Dab20-Ser21-Val22, and an ester linkage is present between D-alloThr18 and Val22 (dhThr: 2-aminobut-2-enoic acid; Dab: 2,4-diaminobutanoic acid). Thus, the toxin is a lipodepsipeptide with 22 amino acids. The mono- and tetraacetate derivatives and two alkaline hydrolysates, compounds A and B, were prepared. We discuss here the structure–activity relationships between the derivatives and their necrotic activities toward lettuce.
- Komatsu, Hidekazu,Shirakawa, Takashi,Uchiyama, Takeo,Hoshino, Tsutomu
-
p. 299 - 309
(2019/02/20)
-
- 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)
-
- Isolation and structure determination of a new cytotoxic peptide, curacozole, from Streptomyces curacoi based on genome mining
-
Using genome mining, a new cytotoxic peptide named curacozole was isolated from Streptomyces curacoi. Through ESI-MS and NMR analyses, curacozole was determined to be a macrocyclic peptide containing two isoleucine, two thiazole and three oxazole moieties. Curacozole exhibited potent cytotoxic activity against HCT116 and HOS cancer cells. The proposed biosynthetic gene cluster of curacozole was identified and compared with that of the related compound YM-216391.
- Kaweewan, Issara,Komaki, Hisayuki,Hemmi, Hikaru,Hoshino, Kanata,Hosaka, Takeshi,Isokawa, Gouchi,Oyoshi, Takanori,Kodani, Shinya
-
-
- Preparation and characterization of a new open-tubular capillary column for enantioseparation by capillary electrochromatography
-
In order to use the enantioseparation capability of cationic cyclodextrin and to combine the advantages of capillary electrochromatography (CEC) with open-tubular (OT) column, in this study, a new OT-CEC, coated with cationic cyclodextrin (1-allylimidazolium-β-cyclodextrin [AI-β-CD]) as chiral stationary phase (CSP), was prepared and applied for enantioseparation. Synthesized AI-β-CD was characterized by infrared (IR) spectrometry and mass spectrometry (MS). The preparation conditions for the AI-β-CD-coated column were optimized with the orthogonal experiment design L9(34). The column prepared was characterized by scanning electron microscopy (SEM) and elemental analysis (EA). The results showed that the thickness of stationary phase in the inner surface of the AI-β-CD-coated columns was about 0.2 to 0.5?μm. The AI-β-CD content in stationary phase based on the EA was approximately 2.77?mmol·m?2. The AI-β-CD-coated columns could separate all 14 chiral compounds (histidine, lysine, arginine, glutamate, aspartic acid, cysteine, serine, valine, isoleucine, phenylalanine, salbutamol, atenolol, ibuprofen, and napropamide) successfully in the study and exhibit excellent reproducibility and stability. We propose that the column, coated with AI-β-CD, has a great potential for enantioseparation in OT-CEC.
- Li, Yingjie,Tang, Yimin,Qin, Shili,Li, Xue,Dai, Qiang,Gao, Lidi
-
p. 283 - 292
(2019/02/05)
-
- Chromatographic Resolution of α-Amino Acids by (R)-(3,3'-Halogen Substituted-1,1'-binaphthyl)-20-crown-6 Stationary Phase in HPLC
-
Three new chiral stationary phases (CSPs) for high-performance liquid chromatography were prepared from R-(3,3'-halogen substituted-1,1'-binaphthyl)-20-crown-6 (halogen = Cl, Br and I). The experimental results showed that R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6 (CSP-1) possesses more prominent enantioselectivity than the two other halogen-substituted crown ether derivatives. All twenty-one α-amino acids have different degrees of separation on R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6-based CSP-1 at room temperature. The enantioselectivity of CSP-1 is also better than those of some commercial R-(1,1'-binaphthyl)-20-crown-6 derivatives. Both the separation factors (α) and the resolution (Rs) are better than those of commercial crown ether-based CSPs [CROWNPAK CR(+) from Daicel] under the same conditions for asparagine, threonine, proline, arginine, serine, histidine and valine, which cannot be separated by commercial CR(+). This study proves the commercial usefulness of the R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6 chiral stationary phase.
- Wu, Peng,Wu, Yuping,Zhang, Junhui,Lu, Zhenyu,Zhang, Mei,Chen, Xuexian,Yuan, Liming
-
supporting information
p. 1037 - 1042
(2017/07/25)
-
- 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.
-
supporting information
p. 2243 - 2249
(2016/10/04)
-
- 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
-
p. 2941 - 2952
(2016/12/07)
-
- 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
-
-
- ｔ-BUTYLKETONE BINAPHTHOL DERIVATIVES AND PREPARING METHOD THEREOF
-
The present disclosure relates to a t-butylketone binaphthol derivative and a method of preparing the same, the t-butylketone binaphthol derivative being a high-efficiency chiral extracting agent which has a very high chiral selectivity enabling to extract an amino acid from an aqueous solution phase to an organic layer and to facilitate its hydrolysis, and enabling a continuous reuse of the organic layer.
- -
-
Paragraph 0097
(2017/01/17)
-
- 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; 0083; 0084
(2015/01/07)
-
- 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)
-
- 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)
-
- SEPARATING AGENT FOR CHROMATOGRAPHY
-
A separating agent for chromatography is provided that is useful for the separation of specific compounds, e.g., for the optical resolution of amino acids. This separating agent for chromatography provides a higher productivity and contains a crown ether-like cyclic structure and optically active binaphthyl. This separating agent for chromatography containing a crown ether-like cyclic structure and optically active binaphthyl is provided by introducing a substitution group for binding to carrier into a specific commercially available 1,1′-binaphthyl derivative that has substituents at the 2, 2′, 3, and 3′ positions, then introducing a crown ether-like cyclic structure, and subsequently chemically bonding the binaphthyl derivative to the carrier through the substitution group for binding to carrier.
- -
-
Paragraph 0074; 0075
(2013/08/15)
-
- Surugamides A-E, cyclic octapeptides with four D-amino acid residues, from a marine streptomyces sp.: LC-MS-aided inspection of partial hydrolysates for the distinction of D- and L-amino acid residues in the sequence
-
Surugamides A-E (1-5), cyclic octapeptides with four d-amino acid residues, were isolated from the broth of marine-derived Streptomyces sp. Their planar structures were determined by analyses of spectroscopic data, and the absolute configuration of constituent amino acid residues was determined by the Marfey's method. Differentiation of d-Ile and l-Ile in the sequence was established by chiral analysis of fragment peptides obtained from the partial hydrolysate, whose identification was conducted by LC-MS/MS.
- Takada, Kentaro,Ninomiya, Akihiro,Naruse, Masato,Sun, Yi,Miyazaki, Masayuki,Nogi, Yuichi,Okada, Shigeru,Matsunaga, Shigeki
-
p. 6746 - 6750
(2013/07/26)
-
- Calyxamides A and B, cytotoxic cyclic peptides from the marine sponge Discodermia calyx
-
Cyclic peptides containing 5-hydroxytryptophan and thiazole moieties were isolated from the marine sponge Discodermia calyx collected near Shikine-jima Island, Japan. The structures of calyxamides A (1) and B (2), including the absolute configurations of all amino acids, were elucidated by spectroscopic analyses and degradation experiments. The structures are similar to keramamides F and G, previously isolated from Theonella sp. The analysis of the 16S rDNA sequences obtained from the metagenomic DNA of D. calyx revealed the presence of Candidatus Entotheonella sp., an unculturable δ-proteobacterium inhabiting the Theonella genus and implicated in the biosynthesis of bioactive peptides.
- Kimura, Miki,Wakimoto, Toshiyuki,Egami, Yoko,Tan, Karen Co,Ise, Yuji,Abe, Ikuro
-
experimental part
p. 290 - 294
(2012/05/05)
-
- Chiral imprinting with amino acids of ordered mesoporous silica exhibiting enantioselectivity after calcination
-
Chiral ordered mesoporous silica (COMS) was synthesized in basic media by combining tetraethyl orthosilicate and quaternized aminosilane (with a templating role) silica sources together with four different standard amino acids (arginine, histidine, isoleucine, and proline). Besides the hexagonal MCM-41-type structure, narrow pore size distribution, and high specific surface area, it was found that these solids have potential for enantiomeric separation because of the transference of chirality from the amino acid to the silica. This is illustrated by the resolution of several racemic mixtures (those of proline, isoleucine, trans-4-hydroxyproline, pipecolic acid, valine, leucine, and phenylglycine) with the calcined COMS prepared with l-proline. The opposite behavior observed in induced circular dichroism experiments with calcined COMS, obtained using both enantiomers of proline, confirmed their chiral nature. The high number and variety of existing amino acids, and chiral organic compounds in general, makes these ordered silicas attractive for the production of enantiopure substances.(Figure Presented)
- Lacasta, Susana,Sebastian, Victor,Casado, Clara,Mayoral, Alvaro,Romero, Pilar,Larrea, Angel,Vispe, Eugenio,Lopez-Ram-De-Viu, Pilar,Uriel, Santiago,Coronas, Joaquin
-
scheme or table
p. 1280 - 1287
(2012/02/15)
-
- 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)
-
- 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)
-
- 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.
- -
-
-
- 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.
- -
-
-
- Process for producing N-formylleucine of high purity
-
A process for producing N-formylleucine includes reacting leucine with formamide, precipitating the N-formylleucine, once the reaction is complete, at a temperature of approximately 0° to 40° C., by mixing the reaction medium with water and an acid, so that the final pH of the mixture is approximately 2 to 3, wherein the amount of water used in between approximately 1.5 and 5 parts per part by weight of starting formamide.
- -
-
-
- 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.
- -
-
-
