- TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids
-
The nociceptor TRPA1 is thought to be activated through covalent modification of specific cysteine residues on the N terminal of the channel. The precise mechanism of covalent modification with unsaturated carbonyl-containing compounds is unclear, therefore by examining a range of compounds which can undergo both conjugate and/or direct addition reactions we sought to further elucidate the mechanism(s) whereby TRPA1 can be activated by covalent modification. Calcium signalling was used to determine the mechanism of activation of TRPA1 expressed in HEK293 cells with a series of related compounds which were capable of either direct and/or conjugate addition processes. These results were confirmed using physiological recordings with isolated vagus nerve preparations. We found negligible channel activation with chemicals which could only react with cysteine residues via conjugate addition such as acrylamide, acrylic acid, and cinnamic acid. Compounds able to react via either conjugate or direct addition, such as acrolein, methyl vinyl ketone, mesityl oxide, acrylic acid NHS ester, cinnamaldehyde and cinnamic acid NHS ester, activated TRPA1 in a concentration dependent manner as did compounds only capable of direct addition, namely propionic acid NHS ester and hydrocinnamic acid NHS ester. These compounds failed to activate TRPV1 expressed in HEK293 cells or mock transfected HEK293 cells. For molecules capable of direct or conjugate additions, the results suggest for the first time that TRPA1 may be activated preferentially by direct addition of the thiol group of TRPA1 cysteines to the agonist carbonyl carbon of α,β-unsaturated carbonyl-containing compounds.
- Sadofsky, Laura R.,Boa, Andrew N.,Maher, Sarah A.,Birrell, Mark A.,Belvisi, Maria G.,Morice, Alyn H.
-
-
Read Online
- A Catalyst-Free Synthesis of Fused Perfluoroalkylated 2,3-Dihydroisoxazoles via Oxa-Michael-Aldol Annulation
-
A novel synthesis of fused perfluoroalkylated 2,3-dihydroisoxazoles is achieved via oxa-Michael-aldol annulation between perfluoroalk- 2-ynoates and N-hydroxyimides. This method provides a convenient route for the synthesis of pyrrolidin-2-one-fused perfluoroalkylated 2,3-dihydroisoxazoles in yields of up to 97%. Diverse and pharmaceutically attractive polycyclic scaffolds can be obtained rapidly and efficiently under these mild, catalyst-free conditions.
- Zhou, Wei,Yao, Lan,Liu, Yongxiurong,Shen, Lichun,Chen, Jie,Deng, Hongmei,Shao, Min,Zhang, Hui,Tang, Xiaojun,Cao, Weiguo
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supporting information
p. 429 - 438
(2021/10/01)
-
- DLL3-TARGETING MULTISPECIFIC ANTIGEN-BINDING MOLECULES AND USES THEREOF
-
The disclosure provides multispecific antigen-binding molecules that comprise a first antigen-binding moiety and a second antigen-binding moiety, each of which is capable of binding to CD3 and CD137, but does not bind to CD3 and CD137 at the same time; and a third antigen-binding moiety that is capable of binding to DLL3, preferably human DLL3, which induce T-cell dependent cytotoxity more efficiently whilst circumventing adverse toxicity concerns or side effects that other multispecific antigen-binding molecules may have. The present invention provides multispecific antigen-binding molecules and pharmaceutical compositions that can treat various cancers, especially those associated with DLL3, by comprising the antigen-binding molecule as an active ingredient.
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-
- A METHOD FOR PREPARING N-SUBSTITUTED SUCCINIMIDE
-
N -substituted succinimides are disclosed. , The 1-substituted succinimide prepared by reacting a succinic acid with 1-order amine is reacted with an acid catalyst, a metal catalyst, and a reducing agent to produce N - N -substituted succinimide, which is industrially useful and can be widely applied to various industrial fields.
- -
-
Paragraph 0089; 0091-0093; 0095-0108; 0113
(2021/10/27)
-
- Synthesis method of N-(benzyloxycarbonyloxy)succinimide
-
The invention relates to a synthesis method of N-(benzyloxycarbonyloxy)succinimide; the invention mainly solves the technical problems of high raw material cost, overhigh reaction rate, severe heat release, high possibility of generating impurities, high product loss during refining and the like in an existing synthesis method. The synthesis method comprises the following steps: dissociating hydroxylamine hydrochloride in an aqueous solution by using NaOH, and carrying out a reaction with succinic anhydride to generate HOSu; carrying out a reaction of HOSu with Cbz-Cl in a mixed solution of water and ethyl acetate to generate a target compound Cbz-OSu. Cbz-OSu is commonly used as a polypeptide commonly used reagent, and a Z-amino protection reagent is selectively introduced in synthesis ofamino acids and aminoglycoside antibiotics.
- -
-
Paragraph 0005; 0008; 0012; 0015
(2020/05/05)
-
- Method for synthesizing 9-fluorenylmethylsuccinimido carbonate by one-pot two-phase method
-
The invention relates to the technical field of organic synthesis, specifically to a method for synthesizing 9-fluorenylmethylsuccinimido carbonate by a one-pot two-phase method. The method comprisesthe following steps: adding purified water and hydroxylamine sulfate into a reaction container, dropwise adding liquid caustic soda under stirring, after the liquid caustic soda is dropwise added, adding butanedioic anhydride in batches, and carrying out high-temperature vacuum dehydration under acid catalysis until no water is extracted out so as to prepare an N-hydroxysuccinimide solution; adding a chloroformic acid-9-fluorenyl methyl ester solution into the N-hydroxysuccinimide solution, and controlling a temperature at 0 to 60 DEG C; after the chloroformic acid-9-fluorenyl methyl ester solution is added, starting to dropwise add an aqueous alkali solution; after the aqueous alkali solution is dropwise added, separating out an organic layer, carrying out concentrating to dryness, and carrying out recrystallizing so as to obtain a 9-fluorenylmethylsuccinimido carbonate finished product. The above-mentioned method provided by the invention innovatively adopts the one-pot two-phase method; a reaction liquid containing N-hydroxysuccinimide is directly used for synthesizing the 9-fluorenylmethylsuccinimido carbonate in a two-phase reaction manner; process steps are effectively reduced; and the method is applicable to large-scale industrial production.
- -
-
Paragraph 0011; 0024-0029
(2020/03/03)
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- Solvent-Controlled Synthesis of Thiocyanated Enaminones and 2-Aminothiazoles from Enaminones, KSCN, and NBS
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An effective and simple solvent-controlled synthesis of thiocyanated enaminones and 2-aminothiazoles has been demonstrated from enaminones, potassium thiocyanate, and N-bromosuccinimide. This process features mild reaction conditions, simple and easy oper
- Chen, Xue,Cuan, Xiaodan,Duan, Xiyan,Li, Huimin,Liu, Kun,Liu, Xiaojing,Wang, Junqin,Wang, Lin,Zhou, Huiyun
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- COMPOUNDS AND METHODS FOR DETECTING EARLY ATHEROSCLEROTIC LESIONS IN BLOOD VESSELS
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A biotin derivative of formula (I) (I) in which R is a peptide with the sequence VHPKQHRGGSKGC, linked to the succinimidyl ring through the -SH group of the C-terminal cysteine, which can be used in a method for detecting early atherosclerotic lesions in the blood vessels of a human subject, which method includes steps of a) forming a complex of this biotin derivative with avidin, neutravidin or streptavidin; b) parenterally administering the complex thus formed; c) subsequently, parenterally administering a chelating agent including a chelating moiety, a biotin moiety and a metal radionuclide, and d) subjecting the human subject to a diagnostic nuclear imaging technique; this biotin derivative can also be used in a method for treating a disease of a human patient characterized by an overexpression of VCAM-1, including inflammatory diseases, atherosclerosis, multiple sclerosis, neurodegenerative diseases and neuroinflammatory diseases.
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Page/Page column 23; 24
(2019/10/04)
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- Preparation method of N-hydroxysuccinimide
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The invention provides a preparation method of N-hydroxysuccinimide, which uses succinic acid as raw materials and reacts with hydroxylamine in the presence of weak acidic substances to prepare the N-hydroxysuccinimide. The reaction yield is over 85 percent, thereby further reducing production cost and eliminating hidden dangers existing in the production process.
- -
-
Paragraph 0034; 0035; 0036; 0038; 0039; 0041; 0042; 0043
(2018/10/19)
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- Preparation method of N-hydroxysuccinimide
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The invention relates to a preparation method of N-hydroxysuccinimide, and belongs to the technical field of synthesis of drug intermediates. In order to solve the problems that an existing drug is high in corrosiveness, severe in pollution and high in equipment requirement, the invention provides a preparation method of N-hydroxysuccinimide. The method comprises the following step: under the existence of a PBS (phosphate buffer solution), performing click chemical reaction on chitosan and N-hydroxysuccinimide-4-azidobenzoate through microwave heating assistance, thus obtaining the N-hydroxysuccinimide. The preparation method can effectively heat the inside of each molecule to generate the click chemical reaction, so that the influence of gradient change of temperature in a reaction process is reduced; therefore, shortening of the reaction time and high conversion rate are realized, and effects of increasing the yield of a product and improving the purity of the product are achieved.
- -
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Paragraph 0016; 0023-0032
(2018/09/12)
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- NON-HUMAN ANIMAL HAVING HUMAN CD3 GENE SUBSTITUTED FOR ENDOGENOUS CD3 GENE
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The present invention provides genetically modified non-human animals which are deficient in at least one or more types of CD3 genes selected from the group consisting of endogenous CD3ε, CD3δ, and CD3γ in its genome and functionally express at least one or more types of human CD3 genes selected from the group consisting of human CD3?, CD3δ, and CD3γ. In the genetically modified non-human animals of the present invention, mature T cell differentiation and production can take place, and immunocompetent cells including T cells can exert their functions. The genetically modified non-human animals of the present invention enable efficient evaluation and screening in the development of therapeutic agents and therapeutic methods that use human CD3-mediated targeted drugs.
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- Metal-Free C(sp3)-H Allylation via Aryl Carboxyl Radicals Enabled by Donor-Acceptor Complex
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The first aryl carboxyl radical generation by the donor-acceptor complex with N-acyloxyphthalimides and Hantzsch esters is reported. Regio- and chemoselective C(sp3)-H bond allylation is enabled by aryl carboxyl radicals with visible light irradiation under mild and metal-free conditions.
- Li, Yang,Zhang, Jing,Li, Defang,Chen, Yiyun
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supporting information
p. 3296 - 3299
(2018/06/11)
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- An Oxygen-Tolerant PET-RAFT Polymerization for Screening Structure–Activity Relationships
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The complexity of polymer–protein interactions makes rational design of the best polymer architecture for any given biointerface extremely challenging, and the high throughput synthesis and screening of polymers has emerged as an attractive alternative. A porphyrin-catalysed photoinduced electron/energy transfer–reversible addition-fragmentation chain-transfer (PET-RAFT) polymerisation was adapted to enable high throughput synthesis of complex polymer architectures in dimethyl sulfoxide (DMSO) on low-volume well plates in the presence of air. The polymerisation system shows remarkable oxygen tolerance, and excellent control of functional 3- and 4-arm star polymers. We then apply this method to investigate the effect of polymer structure on protein binding, in this case to the lectin concanavalin A (ConA). Such an approach could be applied to screen the structure–activity relationships for any number of polymer–protein interactions.
- Gormley, Adam J.,Yeow, Jonathan,Ng, Gervase,Conway, órla,Boyer, Cyrille,Chapman, Robert
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supporting information
p. 1557 - 1562
(2018/01/15)
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- Sulfation made easy: A new versatile donor for enzymatic sulfation by a bacterial arylsulfotransferase
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An efficient and versatile donor for the sulfation by a bacterial arylsulfotransferase of various phenolic acceptor molecules is reported. Most studies in the past used toxic p-nitrophenyl sulfate as a sulfate donor for sulfation by this enzyme. However both the donor and p-nitrophenol are difficult to remove from the sulfated products. This new donor N-hydroxysuccinimide sulfate is easy to synthesize and has the advantage that at pH values above 7 it hydrolyzes to N-hydroxysuccinimide which is a safe compound and can easily be removed. As examples we demonstrated the formation of sulfated resveratrol and synthesized efficiently 3-sulfo-17-β-estradiol and bisphenol A bisulfate. It is likely that many other phenolic compounds are sulfated using this donor.
- Hartog, Aloysius F.,Wever, Ron
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- MULTIVALENT CONSTRUCTS FOR THERAPEUTIC AND DIAGNOSTIC APPLICATIONS
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The invention provides compositions and methods for therapeutic and diagnostic applications.
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- Palladium-Catalyzed Carbonylation of (Hetero)Aryl, Alkenyl and Allyl Halides by Means of N-Hydroxysuccinimidyl Formate as CO Surrogate
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An efficient Pd-catalyzed carbonylation protocol is described for the coupling of a large panel of aryl, heteroaryl, benzyl, vinyl and allyl halides 2 with the unusual N-hydroxysuccinimidyl (NHS) formate 1 as a CO surrogate to afford the corresponding valuable NHS esters 3. High conversion to the coupling products was achieved with up to 98% yield by means of Pd(OAc)2/Xantphos catalyst system.
- Barré, Ana?s,T?nta?, Mihaela-Liliana,Alix, Florent,Gembus, Vincent,Papamica?l, Cyril,Levacher, Vincent
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supporting information
p. 6537 - 6544
(2015/10/05)
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- Ultrasensitive QRS made by supramolecular assembly of functionalized cyclodextrins and graphene for the detection of lung cancer VOC biomarkers
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A novel electronic nose system comprising functionalized β-cyclodextrin wrapped reduced graphene oxide (RGO) sensors with distinct ability of discrimination of a set of volatile organic compounds has been developed. Non-covalent modification of chemically functionalized cyclodextrin with RGO is carried out by using pyrene adamantane as a linker wherever necessary, in order to construct a supramolecular assembly. The chemical functionality on cyclodextrin is varied utilising the principle of selective chemical modification of cyclodextrin. In the present study, the combined benefits of the host-guest inclusion complex formation ability and tunable chemical functionality of cyclodextrin, as well as the high surface area and electrical conductivity of graphene, are utilized for the development of a set of highly selective quantum resistive chemical vapour sensors (QRS), which can be assembled in an electronic nose.
- Nag, Sananda,Duarte, Lisday,Bertrand, Emilie,Celton, Vronique,Castro, Mickal,Choudhary, Veena,Guegan, Philippe,Feller, Jean-Franois
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supporting information
p. 6571 - 6579
(2015/05/20)
-
- 3,4-Dihydroxy-l-phenylalanine as a biomarker of oxidative damage in proteins: Improved detection using cloud-point extraction and HPLC
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Oxidized protein adducts are formed under conditions of oxidative stress and may represent a valuable biomarker for a variety of diseases which share this common aetiology. A suitable candidate biomarker for oxidized proteins is protein-bound 3,4-dihydrox
- McPherson, Peter A.C.,Türemen, Bryn T.
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p. 376 - 381
(2015/01/09)
-
- One-step radiosynthesis of 4-nitrophenyl 2-[18F]fluoropropionate ([18F]NFP); Improved preparation of radiolabeled peptides for PET imaging
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The versatile 18F-labeled prosthetic group, 4-nitrophenyl 2-[18F]fluoropropionate ([18F]NFP), was synthesized in a single step in 45 min from 4-nitrophenyl 2-bromopropionate, with a decay corrected radiochemical yield of 26.2% ± 2.2%. Employing this improved synthesis of [18F]NFP, [18F]GalactoRGD - the current 'gold standard' tracer for imaging the expression of αVβ 3 integrin - was prepared with high specific activity in 90 min and 20% decay corrected radiochemical yield from [18F]fluoride. 4-Nitrophenyl 2-[18F]fluoropropionate ([18F]NFP), was synthesized in a single radiochemical step in 45 minutes and 26% d.c. radiochemical yield from 4-nitrophenyl 2-bromopropionate. Employing this improved synthesis of [18F]NFP, [18F]GalactoRGD was prepared with high specific activity in 90 minutes and 20% d.c. radiochemical yield from [18F]fluoride. Copyright
- Haskali, Mohammad B.,Roselt, Peter D.,Karas, John A.,Noonan, Wayne,Wichmann, Christian W.,Katsifis, Andrew,Hicks, Rodney J.,Hutton, Craig A.
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p. 726 - 730
(2014/01/06)
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- Column chromatography-free solution-phase synthesis of a natural piper-amide-like compound library
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We have achieved an efficient solution-phase parallel synthesis of a library of natural piper-amide-like compounds from the bifunctional β-phosphono-N-hydroxy-succinimidyl ester intermediate. The primary important feature in our study is the construction of natural-product-like molecules through the adaptation of sophisticated organic reactions that create water-soluble byproducts for a chromatography-free purification. This simple and efficient method rapidly provides a combinatorial library of high yield and purity. The library was evaluated against GPCR targets to demonstrate its potential use as a tool for drug discovery and in chemical biology.
- Kiim, Sumin,Lim, Chaemin,Lee, Sukjin,Lee, Seokwoo,Cho, Hyunkyung,Lee, Joo-Youn,Shim, Dong Sup,Park, Hee Dong,Kim, Sanghee
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supporting information
p. 208 - 215
(2013/05/22)
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- Hydrolysis of 3-carboxy-6,8-difluoro-7-hydroxycoumarin (Pacific Blue) succinimidyl ester under acidic and basic conditions
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The highly sensitive technique of microchip capillary electrophoresis (μCE) with laser-induced fluorescence (LIF) detection is under development for future in situ spaceflight missions to search for the organic chemical signatures of life. One fluorescent probe that enables this technology for amine, amino acid, and dipeptide analysis is 3-carboxy-6,8-difluoro-7- hydroxycoumarin (Pacific Blue, PB) succinimidyl ester. Of particular importance is the hydrolysis of PB succinimidyl ester, which precludes long-term aqueous storage during spaceflight and therefore has a significant impact on instrument design and operation. As such, it is important to characterize the chemical stability of this dye to hydrolysis prior to spaceflight. Here, we study the hydrolysis kinetics of the PB succinimidyl ester at pH values between 3 and 10.5 using μCE-LIF. The PB succinimidyl ester has the longest lifetime at pH 4 (7.3 ± 0.1 h), with dramatically shorter half-lives in the basic pH regime. This work represents a first step in the full characterization of this fluorescent probe for spaceflight applications.
- Stockton, Amanda M.,Mora, Maria F.,Cable, Morgan L.,Willis, Peter A.,Davenport, Timothy C.,Tilley, T. Don
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p. 148 - 151,4
(2020/08/24)
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- Efficient and continuous monoacylation with superior selectivity of symmetrical diamines in microreactors
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Efficient and continuous monoacylation of symmetrical diamines performed in microreactors yielded superior selectivity to that predicted by statistical considerations. It is highly valuable that the kinetically controlled product in high yields was achieved without any special catalyst at ambient temperature.
- Maurya, Ram Awatar,Hoang, Phan Huy,Kim, Dong-Pyo
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scheme or table
p. 65 - 68
(2012/03/26)
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- Nucleophilic iron catalysis in transesterifications: Scope and limitations
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Figure presented The ester bond is one of the most common structural motifs found in nature. Apart from the condensation between an acid and an alcohol, transesterifications represent another mechanistic alternative for the preparation of this compound class. The present paper summarizes our most recent investigations in this field, using nucleophilic iron complexes as catalysts for transesterifications under neutral conditions. This new type of metal catalyst complements the existing methodologies, which rely on Lewis acidic metal complexes. Investigations on scope and limitations, stereochemical course, and chemoselectivities will be presented.
- Magens, Silja,Plietker, Bernd
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supporting information; experimental part
p. 3715 - 3721
(2010/08/07)
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- ANTIBODY MOLECULES HAVING BINDING SPECIFICITY FOR HUMAN IL-13
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The invention relates to antibody molecules having specificity for antigenic determinants of human IL-13, therapeutic uses of the antibody molecules and methods for producing said antibody molecules.
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- DERIVATIVES, REAGENTS, AND IMMUNOASSAY FOR DETECTING LEVETIRACETAM
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Levetiracetam (LEV) derivatives, methods for synthesizing LEV derivatives, and immunodiagnostic assays for LEV. The synthesis methods described herein include chirally-selective, liquid-phase synthesis steps to produce selected LEV derivatives in high-yield. LEV derivatives can include operative groups, such as: immunogenic moieties that can be used to prepare anti-LEV antibodies; antigenic moieties that can be used in immunodiagnostic assays for LEV; or tracer moieties that can be used in immunodiagnostic assays. Additionally, the LEV derivatives can be used in immunodiagnostic assays to compete with LEV for anti-LEV antibodies.
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- Hydroxamic acids as a novel family of serine racemase inhibitors: Mechanistic analysis reveals different modes of interaction with the pyridoxal-5′-phosphate cofactor
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Mammalian serine racemase (SR) is a pyridoxal-5′-phosphate (PLP) dependent enzyme responsible for the biosynthesis of the neurotransmitter D-serine, which activates N-methyl-D-aspartate (NMDA) receptors in the CNS. Aberrant regulation of NMDA receptor signaling has been implicated in a variety of neuropathologies, and inhibitors of SR would therefore be a worthwhile tool for further investigation or treatment of such conditions. Here, we identify a series of small aliphatic hydroxamic acids (HAs) that act as potent SR inhibitors. However, specificity studies showed that some of these HAs can act as nonspecific inhibitors of PLP-dependent enzymes. We employed NMR, MS, and UV/vis spectroscopic techniques to reveal that the nonspecific effect is likely due to irreversible interaction of the HA moiety with PLP to form aldoxime species. We also characterize L-aspartic acid β-hydroxamate as a competitive and selective SR inhibitor that could be used as a scaffold for further inhibitor development. 2009 American Chemical Society.
- Hoffman, Hillary E.,Jirásková, Jana,Cígler, Petr,?anda, Miloslav,Schraml, Jan,Konvalinka, Jan
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experimental part
p. 6032 - 6041
(2010/03/24)
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- GLYCOPEPTIDE AND LIPOGLYCOPEPTIDE ANTIBIOTICS WITH IMPROVED SOLUBILITY
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The invention relates to derivatives of glycopeptide and lipoglycopeptide antibiotics possessing one or more polyethylene glycol moieties. These compounds are useful as antibiotics for the prevention and/or the treatment of infections and present a profile improved as a consequence of the ability to reduce the volume of injection and of a diminution of the side effects brought about by the poor solubility of the parent antibiotics, in particular injection-site and infusion related events.
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Page/Page column 111-112
(2008/12/04)
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- PROCESS FOR PRODUCING CYCLIC N-HYDROXYIMIDE COMPOUND
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A cyclic polycarboxylic acid anhydride, a polycarboxylic acid, or a mixture of them is allowed to react with hydroxylamine or a salt thereof in an organic solvent under dewatering conditions to yield a corresponding cyclic N-hydroxyimide compound. The cyclic polycarboxylic acid anhydride can be, for example, succinic anhydride or glutaric anhydride. The polycarboxylic acid can be, for example, succinic acid, glutaric acid, or adipic acid. In this process, the reaction is preferably carried out using an organic solvent capable of undergoing azeotropy with water as all or part of a reaction solvent while removing water from the reaction system by azeotropy with the organic solvent. This process produces a cyclic N-hydroxyimide compound in a good yield from any of a cyclic polycarboxylic acid anhydride and a polycarboxylic acid.
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Page/Page column 14
(2008/06/13)
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- PROCESS FOR OXIDATION OF ORGANIC COMPOUNDS
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A method oxidizes an organic compound with oxygen in the presence of a catalyst, in which the catalyst contains a N-hydroxy- or N-(substituted oxy)-imide compound derivable from at least one selected from a target product, a reaction intermediate, and a reaction byproduct, and the catalyst is produced from at least one component selected from the target product, reaction intermediate, and reaction byproduct each formed as a result of the reaction and is used in the oxidation reaction so as to make up for a loss of the catalyst due to denaturation in the reaction. The method can easily and inexpensively make up for a loss of the catalyst denaturated in the course of reaction.
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Page/Page column 16
(2008/06/13)
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- Displacement assay for detecting ligate-ligand association events
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Described is a method for detection of ligate-ligand association events, the method comprising the steps: providing a modified surface, the modification consisting in the attachment of at least one type of ligate; providing signal ligands; providing a sample having ligands; bringing a defined quantity of the signal ligands into contact with the modified surface and bringing the sample into contact with the modified surface; detecting the signal ligands; and comparing with reference values the values obtained from the detection of the signal ligands.
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- Short-warp peptide dye conjugate as contrast agent for optical diagnostic
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The invention relates to compounds for tumor diagnosis that consist of conjugates of dyes with short-chain peptides, which are derived from vaso-active intestinal peptide, somatostatin or neurotensin, the use of these compounds as optical diagnostic agents, and diagnostic agents that contain these compounds.
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- Technetium or rhenium complexes, radiopharmaceutical products comprising them
-
The invention relates to a technetium or rhenium complex of formula (I): [in-line-formulae][M (R1CS3)2L]??(I) [/in-line-formulae] in which M is Tc or Re, R1 represents an alkyl, cycloalkyl, aralkyl or aryl group which is unsubstituted or substituted by one or more substituents chosen from halogen atoms, the hydroxyl group, alkyl groups and alkoxy groups, and L is a dithiolate ligand, with the exception of the ligand of formula R2CS2 in which R2 is identical to R1. The dithiolate ligand is preferably a dithiocarbamate. The invention also relates to a radiopharmaceutical product comprising a complex of formula (I) with M representing 99Tc, 186Re or 188Re.
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Page column 11
(2010/02/10)
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- Multivalent constructs for therapeutic and diagnostic applications
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The invention provides compositions and methods for therapeutic and diagnostic applications.
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- KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy
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The present invention provides polypeptides, peptide dimer, and multimeric complexes comprising at least one binding moiety for KDR or VEGF/KDR complex, which have a variety of uses wherever treating, detecting, isolating or localizing angiogenesis is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding KDR or VEGF/KDR complex with high affinity (e.g., having a KD1 μM), and dimer and multimeric constructs comprising these polypeptides.
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- Methods for preparing multivalent constructs for therapeutic and diagnostic applications and methods of preparing the same
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Methods for the preparation of multivalent constructs for therapeutic and diagnostic applications are provided. More specifically, novel methods for preparing multivalent constructs comprising the formula A-B-C-D-E-B′-F for therapeutic and diagnostic applications are provided which use a novel linker D comprising, in various embodiments, a dicarboxylic acid derivative such as, e.g., a glutaric acid bis N-hydroxysuccinimidyl ester or a derivative therof; or a diamine derivative. The remaining components in the multivalent construct A-B-C-D-E-B′-F are defined as follows: A is a first peptide, B is a first branching group, C is an optional first spacer, E is an optional second spacer which may be the same as or different from said first spacer C, B′ is an optional second branching group which may be the same as or different from said first branching group B, and F is a second peptide which may be the same as or different from said first peptide A.
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- Mixtures of isobarically labeled analytes and fragments ions derived therefrom
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This invention pertains to mixtures of isobarically labeled analytes and fragment ions thereof.
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- Mixtures of isobarically labeled analytes and fragments ions derived therefrom
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This invention pertains to mixtures of isobarically labeled analytes and fragment ions thereof.
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- KDR and VEGF/KDR binding peptides
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The present invention provides, inter alia, peptides, peptide dimer, and multimeric complexes comprising at least one binding moiety for KDR or VEGF/KDR complex, which have a variety of uses wherever treating, detecting, isolating or localizing angiogenesis is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding KDR or VEGF/KDR complex with high affinity (e.g., having a KD1 μM), and dimer and multimeric constructs comprising these polypeptides.
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- Multivalent constructs for therapeutic and diagnostic applications
-
The invention provides compositions and methods for therapeutic and diagnostic applications.
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- Monomer having electron-withdrawing group and process for preparing the same
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A monomer containing an electron-withdrawing group of the present invention is represented by following Formula (a), (b) or (c): wherein A1, A2, and A3 are each a ring; Ra, Rb, Rc, and Ru are the same or different and are each a hydrogen atom or organic group; at least one of Rs, Rw and Rv, at least one of Rt and Rw1, and at least one of the two Rw2s are each an electron-withdrawing group, and the others are each a hydrogen atom or organic group; W1 is a single bond or linkage group; and n denotes an integer of 2 to 25, where at least two of Ra, Rb, Rc, Rs, Rt, Ru, Rv, Rw, Rw1, Rw2, W1, and carbon atoms constituting ring A1, carbon atoms constituting ring A2, and carbon atoms constituting ring A3 may be combined to form a ring, respectively. The electron-withdrawing groups in Rs, Rt, Rv, Rw, Rw1, and Rw2 are, for example, groups each containing a fluorine atom. The monomer is useful as a raw material for photoresist polymeric compounds.
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- Development of an enzyme-linked immunosorbent assay for the organophosphorus insecticide bromophos-ethyl
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A competitive enzyme-linked immunosorbent assay (ELISA) was developed for the quantitative detection of the organophosphorus insecticide bromophos-ethyl. Four bromophos-ethyl derivatives (haptens) were synthesized and were coupled to carrier proteins through the pesticide thiophosphate group to use as an immunogen or as a coating antigen. Rabbits were immunized with either one of two haptens coupled to bovine serum albumin for production of polyclonal antibodies, and the sera were screened against one of the haptens coupled to ovalbumin. Using the serum with highest titer, an antigen-coated ELISA was developed, which showed an IC50 of 3.9 ng/mL with a detection limit of 0.3 ng/mL (20% inhibition). An antibody-coated ELISA using an enzyme tracer was also developed, which showed an IC50 of 6.5 ng/mL with a detection limit of 1.0 ng/mL (20% inhibition). The antibodies showed negligible cross-reactivity with other organophosphorus pesticides except with the insecticides bromophos-methyl and chlorpyrifos in the antibody-coated assay only. Recoveries of bromophosethyl from fortified crop and water samples ranged from 82 to 128% and from 95 to 127%, respectively.
- Kim, Kwang-Ok,Kim, Yoo Jung,Lee, Yong Tae,Hammock, Bruce D.,Lee, Hye-Sung
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p. 6675 - 6682
(2007/10/03)
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- Mild and convenient one pot synthesis of N-hydroxyimides from N-unsubstituted imides
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A new, one pot synthesis of various N-hydroxyimides from N-unsubstituted imides is described. Imides are first transformed into their N-Boc derivatives, which are next reacted with aqueous hydroxylamine, providing crystalline hydroxylammonium salts of the corresponding N-hydroxyimides. Filtration and acidic workup affords pure N-hydroxyimides.
- Einhorn,Einhorn,Marcadal-Abbadi
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p. 741 - 748
(2007/10/03)
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- Compositions and methods for cell transformation
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The present invention relates to methods and compositions for the transformation of cells. In particular, compositions and methods are disclosed which include combinations of the nucleic acid of interest and polyhydroxylated or polyglycosylated steroid molecules. Most preferably, exogenous or endogenous nucleic acid is contacted with the cell in the presence of a bile acid (e.g., cholic acid) derivatized with an amine-containing side chain.
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- Methods and compositions for producing novel conjugates of thrombin inhibitors and endogenous carriers resulting in anti-thrombins with extended lifetimes
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Novel compounds comprising chemically reactive intermediates which can react with available reactive functionalities on blood components to form covalent linkages, where the resulting covalently-bound conjugates are found to have thrombin inhibition activity are provided. Specifically, the thrombin inhibitor compounds of the present invention are derivatives of the known thrombin inhibitor argatroban, which can be covalently linked to chemically reactive functionalities on various blood components. The conjugated thrombin inhibitors thereby have extended lifetimes in the bloodstream, as compared to the unconjugated parent drug, and are, therefore, capable of maintaining thrombin inhibitory activity for extended periods of time as compared to the unconjugated parent drug. Also provided herein are methods for inhibiting thrombin activity in vivo comprising administering to the bloodstream of a mammalian host the novel compounds of the present invention.
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- 2'-and/or 7-substituted taxanes
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2'- and/or 7'- substituted taxoid derivatives having improved water-solubility and/or enhanced therapeutic activity and methods of making the same are disclosed.
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- Benzolactam derivatives
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A benzolactam derivative represented by the following formula (I): STR1 wherein n represents an integer of from 1 to 3; R 1 represents a straight- or branched-chain alkyl group or an aralkyl group; R 2 represents a straight- or branched-chain alkyl group; R 3 and R 4 independently represent a hydrogen atom or a straight- or branched-chain alkyl group, and when R 3 and R 4 are adjacent each other on the phenyl group, they may be combined to form a cycloalkyl ring together with two carbon atoms of the phenyl group to which R 3 and R 4 bind, and said cycloalkyl ring may optionally have one or more substituents; and a anti-retroviral agent comprising the same as an active ingredient.
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- A novel linkage for the solid-phase synthesis of hydroxamic acid
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A novel linkage for the solid-phase synthesis of hydroxamic acids is described and its facile application for the solid phase synthesis of peptidyl, succinyl and urea-type hydroxamic acids is illustrated. Cleavage is induced under mild acidic conditions by treatment with formic acid in THF, providing hydroxamic acids in high purity and fair to good yields.
- Bauer, Udo,Ho, Wen-Bin,Koskinen, Ari M.P.
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p. 7233 - 7236
(2007/10/03)
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- Chemically defined polymeric carriers for release of covalently linked agents
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A chemically defined polymeric carrier comprising a series of α-amino acids in any combination containing side chains to which diagnostic/therapeutic and chelating agents can be covalently joined through cleavable linkers either directly or covalently joined through cleavable linkers after chemical modification of the side chains. Hydrazone, disulfide, and ester linkages in any combination can be present in the polymeric carrier between the side chains of the α-amino acids and the agents. The presence of a particular covalent linkage between the side chain and the agent in the carrier is determined by the functional group present in the side chain of the α-amino acid and the functional group present in the agent. The α-amino acids with side chains to which agents do not covalently join can function as spacers to minimize interaction between bulky molecules attached to the polymeric carrier. In addition, those α-amino acids with charged or hydrophilic side chains to which agents do not covalently join can provide increased solubility to the polymeric carrier.
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- Inverse linkage oligonucleotides for chemical and enzymatic processes
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Inverse Linkage Oligonucleotides ("ILO") useful in enzymatic process are disclosed. Particularly preferred ILOs are amenable to enzymatic elongation from either, or most preferably, both termini. In a particularly preferred embodiment, each terminus of an ILO has an enzymatically functional 3' group. Accordingly, under appropriate conditions and in the presence of, e.g., dNTPs, enzyme, sample DNA, and ILO comprising a first region complementary to a first region of the sample DNA and a second region complementary to a second, different region of the sample DNA, exponential amplification of the sample DNA can be effectuated.
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