- Skeletal Analogues of UCS1025A and B by Cyclization of Maleimides: Synthesis and Biological Activity
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Application of a direct ring-closing approach which exploits an intramolecular aldol reaction with a ketene silyl acetal onto a remote imide function leading to the core skeleton of UCS1025A and B effectively provides access to small library of substituted analogues; of interest is their complete lack of antibacterial activity against MRSA (Gram+) and E. coli (Gram-) bacterial strains.
- Ibbotson, Lewis T.,Christensen, Kirsten E.,Genov, Miroslav,Pretsch, Alexander,Pretsch, Dagmar,Moloney, Mark G.
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p. 396 - 400
(2022/02/10)
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- Synthesis of desmosine-BSA/KLH conjugates via Sonogashira/Negishi cross-coupling reactions
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Desmosine is an elastin crosslinking amino acid that is expected to be a useful biomarker of diseases related to elastin degradation including chronic obstructive pulmonary disease (COPD). In this study, conjugates of desmosine and carrier proteins, such
- Miyagi, Seiya,Yokoo, Reiko,Tanigawa, Takahiro,Pitna, Dinda B.,Hirose, Mika,Usuki, Toyonobu
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supporting information
(2022/01/14)
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- CONJUGATES OF A CELL-BINDING MOLECULE WITH CAMPTOTHECIN ANALOGS
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Provided are conjugates of camptothecin analogs with a cell-binding molecule of formula (I), wherein R1, R2, R3, R4, R5, X, L, n, m, T and ----- are defined herein. It also provides methods of making the conjugates of camptothecin analogs to a cell-binding agent, as well as methods of using the conjugates in targeted treatment of cancer, infection, and immunological disorders.
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Page/Page column 201-202
(2021/10/30)
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- A CONJUGATE OF AN AMANITA TOXIN WITH BRANCHED LINKERS
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Provided herein is the conjugation of an amanita toxin compound to a cell-binding molecule with branched linkers for having better targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of an amanita molecule to a cell-binding ligand, as well as methods of using the conjugate in targets treatment of cancer, infection and autoimmune disease.
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Page/Page column 161
(2020/08/22)
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- A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS
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Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.
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Page/Page column 270
(2021/01/23)
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- A CONJUGATE OF A TUBULYSIN ANALOG WITH BRANCHED LINKERS
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The present invention relates to the conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.
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Paragraph 000319; 000320
(2021/03/02)
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- A CONJUGATE OF A TUBULYSIN ANALOG WITH BRANCHED LINKERS
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The present invention relates to the conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.
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Page/Page column 10; 172-173
(2019/07/17)
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- Amide compounds for regulating WNT signal channel and application of compounds
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The invention belongs to the technical field of medicine, and particularly relates to amide compounds for regulating a WNT signal channel and an application of the compounds. The compounds have a structure represented by a general formula I shown in the description.
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-
Paragraph 0257; 0259
(2019/07/11)
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- Depletion of protein thiols and the accumulation of oxidized thioredoxin in Parkinsonism disclosed by a red-emitting and environment-sensitive probe
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Protein sulfhydryl groups play a vital role in maintaining cellular redox homeostasis and protein functions and have attracted increasing interests for the selective detection of protein thiols over low-molecular-weight thiols (LMWTs). Herein, we reported a red-emitting and environment-sensitive probe (FM-red) for detecting and labeling protein thiols. The probe contains a maleimide unit as a thiol receptor and an environment-sensitive fluorophore as a sensor. The emission signal of the probe was exclusively switched on by binding to protein sulfhydryl groups through the twisted intramolecular charge transfer mechanism, while negligible fluorescence was observed when FM-red reacted with LMWTs. Various experiments verified that FM-red possessed fast responsivity (~10 min) and high selectivity to sense protein thiols over LMWTs with a red emission (~655 nm). These favorable properties enable the probe to image protein sulfhydryl groups in live cells and in vivo. In addition, as FM-red has a relatively high molecular weight (MW 688), it is able to separate the labeled proteins from the unlabeled ones after FM-red derivatization via routine protein electrophoresis, which may be applied to determine the redox states of thioredoxin, a small redox protein ubiquitous in all cells. With the aid of the probe, we demonstrated a significant decrease in the protein thiols and the accumulation of oxidized thioredoxin in a cellular model of Parkinson's disease.
- Hu, Guodong,Zhang, Baoxin,Zhou, Pengcheng,Hou, Yanan,Jia, Huiyi,Liu, Yuxin,Gan, Lu,Zhang, Hong,Mao, Yiheng,Fang, Jianguo
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supporting information
p. 2696 - 2702
(2019/04/30)
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- Photopolymerization of maleimide perfluoropolyalkylethers without a photoinitiator
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Perfluoropolyalkylethers derived from hexafluoropropylene oxide were functionalized with maleimide groups. Irradiated by UV-light, the new maleimide macromonomers demonstrated very fast polymerization kinetics with a curing time as fast as 8 s. The effect on photopolymerization of different features such as the molecular weight of the fluorinated chain and the chain length of the hydrogenated spacer were studied, as well as the influence of the type of photoinitiator and the presence of air. Thermal and surface properties of the UV-cured polymers were examined and were typical to fluoropolymers in view of water–oil repellent coatings.
- Bonneaud, Céline,Burgess, Julia M.,Bongiovanni, Roberta,Joly-Duhamel, Christine,Friesen, Chadron M.
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p. 699 - 707
(2019/01/04)
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- Synthesis N - maleic imide-based arylalkylic and its succinyl eater of method
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The invention provides a method for synthesizing N-maleimidoalkyl acid and succinimido ester thereof, which comprises the following steps: (a) carrying out cyclization reaction on a compound disclosed as Formula (II) and phenyl 4-nitrotrifluoroacetate in an organic solvent in the presence of alkali to obtain N-maleimidoalkyl acid disclosed as Formula (III); and (b) reacting the N-maleimidoalkyl acid disclosed as Formula (III) and an acylation reagent in an organic solvent at reflux temperature to obtain an acyl chloride intermediate disclosed as (IV), reacting the acyl chloride intermediate disclosed as (IV) with N-hydroxy succinimide in an organic solvent in the presence of alkali to obtain the N-maleimidoalkyl acid succinimido ester disclosed as Formula (V). The method has the advantages of simple technique, high yield and high product purity, and is suitable for industrial production. The reaction route is disclosed in the specification.
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Paragraph 0063-0066
(2017/10/13)
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- Potent irreversible inhibitors of LasR quorum sensing in Pseudomonas aeruginosa
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Antagonism of quorum sensing represents a promising new antivirulence approach for the treatment of bacterial infection. The development of a novel series of non-natural irreversible antagonists of P. aeruginosa LasR is described. The lead compounds identified (25 and 28) display potent LasR antagonist activity and inhibit expression of the P. aeruginosa virulence factors pyocyanin and biofilm formation in PAO1 and PA14.
- O'Brien, Kevin T.,Noto, Joseph G.,Nichols-O'Neill, Luke,Perez, Lark J.
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p. 162 - 167
(2015/03/04)
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- Azide-alkyne cycloaddition for universal post-synthetic modifications of nucleic acids and effective synthesis of bioactive nucleic acid conjugates
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The regioselective post-synthetic modifications of nucleic acids are essential to studies of these molecules for science and applications. Here we report a facile universal approach by harnessing versatile phosphoramidation reactions to regioselectively incorporate alkynyl/azido groups into post-synthetic nucleic acids primed with phosphate at the 5′ termini. With and without the presence of copper, the modified nucleic acids were subjected to azide-alkyne cycloaddition to afford various nucleic acid conjugates including a peptide-oligonucleotide conjugate (POC) with high yield. The POC was inoculated with human A549 cells and demonstrated excellent cell-penetrating ability despite cell deformation caused by a small amount of residual copper chelated to the POC. The combination of phosphoramidation and azide-alkyne cycloaddition reactions thus provides a universal regioselective strategy to post-synthetically modify nucleic acids. This study also explicated the toxicity of residual copper in synthesized bioconjugates destined for biological systems. This journal is the Partner Organisations 2014.
- Su, Yu-Chih,Lo, Yu-Lun,Hwang, Chi-Ching,Wang, Li-Fang,Wu, Min Hui,Wang, Eng-Chi,Wang, Yun-Ming,Wang, Tzu-Pin
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p. 6624 - 6633
(2014/08/18)
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- CYTOTOXIC-DRUG DELIVERING MOLECULES TARGETING HIV (CDM-HS), CYTOTOXIC ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS AND METHODS OF USE
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The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as CDM-Hs, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by introducing cytotoxic moieties to gp120-expressing cells, thereby causing cell death and preventing cell infection and spread of HIV. It is shown that CDM-Hs bind to gp120 and gp-120 expressing cells competitively with CD4, and these compounds cause cell death of HIV-infected cells, thereby decreasing viral infectivity. Compounds and methods are described herein.
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- Structure-reactivity relationships in a recognition mediated [3+2] dipolar cycloaddition reaction
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The [3+2] dipolar cycloaddition between an azide and maleimide can be accelerated by a factor of more than 100 simply by attaching complementary recognition sites to the reactive partners. This rate acceleration derives from the formation of a reactive bi
- Sinclair, Andrew J.,Del Amo, Vicente,Philp, Douglas
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supporting information; experimental part
p. 3308 - 3318
(2009/10/23)
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- Practical synthesis of maleimides and coumarin-linked probes for protein and antibody labelling via reduction of native disulfides
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The cellular tracking, detection and sensing of protein or antibody movement are important aspects to advance our understanding of biomolecular interactions and activity. Antibodies modified with fluorescent dyes are also valuable tools, especially in immunology research. We describe here a proof-of-principle study of a new water-soluble coumarin probe with a maleimide thiol-reacting unit to fluorescently tag biomolecules. Highlights include: (1) a convenient water-based preparation of N-substituted maleimides, (2) a one-pot preparation of activated maleimido-esters, and (3) a bio-conjugation protocol for the selenol-promoted reduction of native disulfide bonds and the 'site-specific' labelling of antibodies with no significant loss of activity.
- Song, Hong Y.,Ngai, Mun H.,Song, Zhen Y.,MacAry, Paul A.,Hobley, Jonathan,Lear, Martin J.
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experimental part
p. 3400 - 3406
(2010/01/06)
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- Synthesis of 4-maleimidobutyric acid and related maleimides
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Maleimidoalkanoic acids and their activated derivatives, such as their N-hydroxysuccinimide esters, are important, though expensive, linkers for the conjugation of biomolecules. During our synthesis of UCS1025A, we have developed a chromatography-free preparation of 4-maleimidobutyric acid on a one-mole scale. Georg Thieme Verlag Stuttgart.
- De Figueiredo, Renata Marcia,Oczipka, Philipp,Froehlich, Roland,Christmann, Mathias
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p. 1316 - 1318
(2008/12/22)
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- Design and synthesis of a novel DNA-encoded chemical library using Diels-Alder cycloadditions
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DNA-encoded chemical libraries are increasingly being employed for the identification of binding molecules to protein targets of pharmaceutical relevance. Here, we describe the synthesis and characterization of a DNA-encoded chemical library, consisting of 4000 compounds generated by Diels-Alder cycloaddition reactions. The compounds were encoded with unique DNA fragments which were generated through a stepwise assembly process and serve as amplifiable bar codes for the identification and relative quantification of library members.
- Buller, Fabian,Mannocci, Luca,Zhang, Yixin,Dumelin, Christoph E.,Scheuermann, Joerg,Neri, Dario
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supporting information; experimental part
p. 5926 - 5931
(2009/05/31)
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- Probing selectivity in recognition-mediated dynamic covalent processes
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Two simple recognition-mediated dynamic Diels-Alder systems are used to probe the role of kinetics and thermodynamics in determining the equilibrium position in exchanging libraries and the time taken to reach that equilibrium. The selectivity expressed by recognition-driven dynamic processes is demonstrated to be less than the free-energy difference between the components as a result of compensatory effects arising from the extent of conversion to products within the library.
- Bennes, Raphael M.,Philp, Douglas
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p. 3651 - 3654
(2007/10/03)
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- NEW EFFECTOR CONJUGATES, PROCESS FOR THEIR PRODUCTION AND THEIR PHARMACEUTICAL USE
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Conjugates of epothilones and epothilone derivatives (as effectors) with suitable biomolecules (as recognition units) are described. Their production is carried out by the effectors being reacted with suitable linkers, and the compounds that are produced are conjugated to the recognition units. The pharmaceutical use of the conjugates for treating proliferative or angiogenesis-associated processes is described.
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Page/Page column 45-46
(2010/02/06)
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- Solid phase-solid state synthesis of N-alkyl imides from anhydrides
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Preparation of N-alkyl imides from anhydrides is developed on polymer support in solid state assisted by microwave for the first time.
- Chandrasekhar,Padmaja,Raza
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p. 1597 - 1599
(2007/10/03)
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