- Synthetic micelle sensitive to IR light via a two-photon process
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A micellar assembly of molecules constituted of poly(ethylene glycol) as the hydrophilic component and 2-diazo-1,2-naphthoquinone as the hydrophobic component was shown to be destroyed in a two-photon photoreaction triggered by infrared light with release of an encapsulated fluorescent probe molecule. Copyright
- Goodwin, Andrew P.,Mynar, Justin L.,Ma, Yingzhong,Fleming, Graham R.,Frechet, Jean M. J.
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Read Online
- Molecular recognition of histidine-tagged molecules by metal-chelating lipids monitored by fluorescence energy transfer and correlation spectroscopy
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Complex binding of proteins by metal-chelating lipids via surface- exposed or protein-engineered histidines provides an universal and powerful concept for the orientation and two-dimensional crystallization of proteins at self-organized interfaces. To dem
- Dorn, Ingmar T.,Neumaier, Klaus R.,Tampé, Robert
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Read Online
- Preparation and application of three-branch RGD modified brain glioma targeting lipid material
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The invention discloses a three-branch RGD-modified glioma targeting lipid material which is used for targeted delivery of brain glioma treatment drugs. One end of the novel lipid material is connected with cholesterol extending through polyethylene glycol, and the other end of the novel lipid material is connected with RGD peptide with brain glioma targeting function, and the novel lipid material can be used for integrin receptor α which is highly expressed on the surface of brain capillary endothelial cells and brain glioma cells. v β3 The affinity between the brain glioma is achieved through the affinity between the brain glioma, and the effective concentration of the therapeutic drug to the brain tumor is improved. The novel lipid lipid material can be used for liposome. The prepared paclitaxel liposome has obvious brain targeting property and tumor targeting property, and has wide application prospects.
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Paragraph 02=021
(2021/11/03)
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- HDAC DEGRADER
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The disclosure provides compounds of formula (I). The compounds may be used to degrade the Histone Deacetylase (HDAC) family of enzymes, particularly HDAC1, 2 and 3 that exist in corepressor complexes. Accordingly, the compounds may
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Page/Page column 37; 71-72
(2021/07/31)
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- PROTAC-mediated degradation of class i histone deacetylase enzymes in corepressor complexes
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We have identified a proteolysis targeting chimera (PROTAC) of class I HDACs 1, 2 and 3. The most active degrader consists of a benzamide HDAC inhibitor, an alkyl linker, and the von Hippel-Lindau E3 ligand. Our PROTAC increased histone acetylation levels and compromised colon cancer HCT116 cell viability, establishing a degradation strategy as an alternative to class I HDAC inhibition.
- Adams, Grace E.,Cowley, Shaun Michael,Hodgkinson, James T.,Millard, Christopher J.,Norris, James K. S.,Schwabe, John W. R.,Smalley, Joshua P.,Song, Yun
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supporting information
p. 4476 - 4479
(2020/05/13)
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- BIVALENT TARGETED CONJUGATES
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The invention provides conjugates that comprise a bivalent targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates, compositions comprising the bidentate targeting ligands and the conjugates, as well as methods for targeting therapeutic nucleic acids with the bidentate conjugates. The conjugates are useful to target therapeutic nucleic acids.
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Page/Page column 71; 72
(2020/05/28)
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- THERAPEUTIC METHODS
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The invention provides methods and compositions for delivering a nucleic acid to a cell or the cytosol of the target cell. The method includes contacting the cell with, 1) a membrane-destabilizing polymer; and 2) a nucleic acid conjugate. The nucleic acid conjugate includes a targeting ligand bound to an optional linker and a nucleic acid.
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Page/Page column 204; 243; 244-245
(2020/05/28)
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 1986; 1987
(2019/07/10)
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- COMPOUNDS AND METHODS FOR OPTICAL SENSING OF ELECTRICAL ACTIVITY IN BIOLOGICAL SYSTEMS
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Disclosed are tethered chromophore compositions comprising a membrane-spanning tether. The compounds can include covalently tethered fluorophore-quencher combinations useful for measuring action potentials and other fast electrical events in cells and tissues.
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Paragraph 0095
(2019/08/20)
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- Diosgenin-3-derivative as well as preparation method and application thereof
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The invention relates to a diosgenin-3-derivative as well as a preparation method and application thereof. The diosgenin-3-derivative shown as a formula I provided by the invention has a structural formula shown in the description, wherein R1 is amino straight-chain fatty acid residue or amino acid residue; R2 is H or a structural formula shown in the description; R3 is H, C1-C18 alkyl or phenyl.The derivative disclosed by the invention is rich in raw material source, simple and convenient in synthetic route, high in yield and suitable for large-scale production; the derivative has excellentantitumor activity and is superior to diosgenin.
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Paragraph 0038-0041; 0046-0049
(2018/03/26)
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- Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane
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The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion. Two fluorescent analogues (compound 29 with 4-amino-naphthalimide and 34 with 4-nitrobenz-2-oxa-1,3-diazole fluorophores) with good activity (MIC = 0.5 μg/mL against MRSA) were also constructed and confocal microscopy studies indicate that the primary site of interaction for this family of compounds is the bacterial membrane.
- Hickey, Shane M.,Ashton, Trent D.,Boer, Gareth,Bader, Christie A.,Thomas, Michael,Elliott, Alysha G.,Schmuck, Carsten,Yu, Heidi Y.,Li, Jian,Nation, Roger L.,Cooper, Matthew A.,Plush, Sally E.,Brooks, Douglas A.,Pfeffer, Frederick M.
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supporting information
p. 9 - 22
(2018/10/20)
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- COMPOUNDS, COMPOSITONS AND METHODS RELATED TO ANTIMICROBIAL APPLICATIONS
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The present disclosure is in the field of polymers and pharmaceuticals/antimicrobials. The disclosure provides compounds based on SNAP (synthetic novel antimicrobial polymer) technology, compositions and methods of managing microbial infections including surgical site infections (SSIs). The present compounds are used as a management/therapeutic strategy to target microbial infections and have advantages including excellent antimicrobial potency, biofilm disruption ability, broad spectrum activity against various organisms covering both gram negative and gram positive bacteria as well as fungal pathogens, and low toxicity profile to ensure a healthy therapeutic window for use in humans.
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Page/Page column 100-101
(2018/03/25)
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- Synthesis, characterization, and biological studies of diosgenyl analogs
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A series of diosgenyl analogs were prepared from diosgenin to evaluate their anticancer activity and antithrombotic property. Analog 4, which had a spiroketal structure with a 6-aminohexanoic acid residue, exhibited the highest potency against all five tumor cell lines. It significantly blocked tumor growth, induced cell apoptosis and autophagy, and regulated cellular calcium concentration, mitochondrial membrane potential, adenosine triphosphate, and cell cycle. In addition, fluorescence-tagged compounds indicated that the analogs could rapidly accumulate in the cytoplasm, but no specific localization in the nucleus of cancer cells was observed. Furthermore, preliminary structure–activity relationship studies demonstrated that spiroketal analogs exhibit better antithrombotic activity than furostanic analogs, which exhibit the opposite effect by promoting thrombosis. Our study indicates that compound 4 may be a promising anticancer drug candidate for cancer patients with thromboembolism.
- Huang, Bao-Zhan,Xin, Guang,Ma, Li-Mei,Wei, Ze-Liang,Shen, Yan,Zhang, Rui,Zheng, Hua-Jie,Zhang, Xiang-Hua,Niu, Hai,Huang, Wen
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p. 272 - 298
(2017/03/17)
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- Graphene Oxide Cellular Delivery of Hydrophilic Small Molecules
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Unmodified graphene oxide conjugated with hydrophilic small molecules for cellular delivery.
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Paragraph 0075; 0076
(2017/04/04)
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- Regulating competing supramolecular interactions using ligand concentration
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The complexity of biomolecular systems inevitably leads to a degree of competition between the noncovalent interactions involved. However, the outcome of biological processes is generally very well-defined often due to the competition of these interaction
- Teunissen, Abraham J. P.,Paffen, Tim F. E.,Ercolani, Gianfranco,De Greef, Tom F. A.,Meijer
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supporting information
p. 6852 - 6860
(2016/06/14)
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- PHARMACEUTICAL COMPOSITION FOR RESPIRATORY ADMINISTRATION
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The present invention provides a pharmaceutical composition for respiratory administration containing a polysaccharide derivative having a group derived from a polysaccharide and a group derived from a physiologically active substance that is covalently b
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Paragraph 0246
(2016/06/28)
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- ANTIBACTERIAL AGENTS
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The invention provides an antibacterial compound of formula (I) or a salt thereof, as well as an antibacterial compound of formula (II) or a salt thereof, wherein R1, R2, X, Y and n have any of the values defined in the specification.
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Page/Page column 29; 30; 36
(2016/05/09)
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- Multiple-stimulus-responsive supramolecular gels and regulation of chiral twists: The effect of spacer length
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Abstract A new class of homologous gelators, LG12-(CH2)n-BSA, composed of bipyridinyl groups, L-glutamic moieties having double dodecyl chains, and linked alkyl spacers with different lengths were synthesized. It was found that these gelators could immobilize medium-polarity solvents readily and the behaviors of these gels showed a dependence on the spacer length. Of all the gels, the LG12-(CH2)11-BSA gels exhibited self-healing property and multiple-stimulus responsibility, such as heating, shaking, and sonication. The investigation of CD spectra indicated that the supramolecular chirality, which was attributed to the chiral transfer from the chiral center to the assemblies, was also closely related to the length of methylene spacers. The longer the alkyl spacers, the weaker the transmitted supramolecular chirality. Only LG12-(CH2)1-BSA gelators, which had the shortest spacers, formed right-handed nanoscale chiral twists owing to crowded hydrogen bonding interactions. Moreover, the high-polarity solvent DMF was found to be able to regulate the chiral twist as well as its pitch length readily. A new twist on healing: Self-healing supramolecular gels that are responsive to multiple stimuli were developed. The formation of nanoscale twists could be controlled by the length of the methylene spacers of the gelator molecules. The pitch of these twists could be regulated by DMF.
- Miao, Wangen,Yang, Dong,Liu, Minghua
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p. 7562 - 7570
(2015/05/13)
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- Synthesis and pharmacological evaluation of dual acting ligands targeting the adenosine A2A and dopamine D2 receptors for the potential treatment of parkinsons disease
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A relatively new strategy in drug discovery is the development of dual acting ligands. These molecules are potentially able to interact at two orthosteric binding sites of a heterodimer simultaneously, possibly resulting in enhanced subtype selectivity, higher affinity, enhanced or modified physiological response, and reduced reliance on multiple drug administration regimens. In this study, we have successfully synthesized a series of classical heterobivalent ligands as well as a series of more integrated and drug-like dual acting molecules, incorporating ropinirole as a dopamine D2 receptor agonist and ZM 241385 as an adenosine A2A receptor antagonist. The best compounds of our series maintained the potency of the original pharmacophores at both receptors (adenosine A2A and dopamine D2). In addition, the integrated dual acting ligands also showed promising results in preliminary blood-brain barrier permeability tests, whereas the classical heterobivalent ligands are potentially more suited as pharmacological tools.
- J?rg, Manuela,May, Lauren T.,Mak, Frankie S.,Lee, Kiew Ching K.,Miller, Neil D.,Scammells, Peter J.,Capuano, Ben
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p. 718 - 738
(2015/01/30)
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- METHODS OF MAKING CANCER COMPOSITIONS
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Provided herein are methods of making the compound of Formula I and certain intermediates involved in such process.
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- Functionalised nanoparticles, their production and use
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Stable complexes are described, formed by mono- and di-functional compounds bound to nanoparticles composed of various types of transition metal oxides and of metals useful in the production processes of different types of new materials (such as for examp
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Page/Page column 5
(2014/09/03)
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- Reagent for introduction of protein or gene
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The present invention provides a reagent for introducing a protein or gene into a cell. The reagent of the present invention is, for example, a reagent for introducing a protein or gene into a cell, which comprises a composition comprising a cationic amino acid type lipid represented by the following formula (I)-1: (wherein in formula (I)-1: L is a single bond, —CONH—, or —S—S—; M1 is —(CH2)k— or —(CH2CH2O)k— (wherein k is an integer between 0 and 14); and m1 and m2 are each independently an integer between 11 and 21 (in this regard, when providing a reagent for introducing a gene into a cell, the case where both m1 and m2 are 15 is excluded)).
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Page/Page column 34
(2013/02/28)
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- FUNCTIONALISED NANOPARTICLES, THEIR PRODUCTION AND USE
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Stable complexes are described, formed by mono- and di-functional compounds bound to nanoparticles composed of various types of transition metal oxides and of metals useful in the production processes of different types of new materials (such as for examp
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Page/Page column 5
(2012/07/27)
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- Synthesis and evaluation of fully (5-amidoisophthalic acid)-functionalised polyacrylamides as selective inhibitors of the beta crystal polymorph of L-glutamic acid
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Poly-N-5-acrylamidoisophthalic acid (4), poly-N-(5-(N-(3,5-dicarboxyphenyl) carbamoyl)pentyl)acryl-amide (10a) and poly-N-(11-(N-(3,5-dicarboxyphenyl) carbamoyl)undecyl)acrylamide (10b) were prepared and assessed as polymorph-selective crystallization inhibitors of the stable b form of L-glutamic acid.Polymerization was carried out as the final step in the preparation of 10a and 10b to ensure the preparation of fully functionalized polymers.Polymers 4, 10a and 10b were effective as complete inhibitors of the stable b form of L-glutamic acid in quantities of 0.5% w/w or greater, whereas the corresponding 'monomeric' additives 2 and 11 required quantities of 3% or greater to completely inhibit the b form, demonstrating a cooperative binding effect by the polymeric additives.Within the series of polymers 4, 10a and 10b, polymer 10a, which features a short tethering chain, was the most effective.
- Kelly, Dawn M.,Moynihan, Humphrey A.
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experimental part
p. 5459 - 5466
(2010/08/13)
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- Incorporation of fluorescent-labeled non-α-amino carboxylic acids into the N-terminus of proteins in response to amber initiation codon
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Incorporation of non-natural amino acid derivatives containing fluorescent groups into proteins is a useful method for protein analyses. Here, we investigated the incorporation of fluorescent-labeled non-α-amino carboxylic acids into the N-terminus of proteins in response to the UAG initiation codon. A series of TAMRA-labeled amino carboxylic acids were synthesized and attached to an amber suppressor initiator tRNA derived from Escherichia coli initiator tRNA. Fluorescent-labeled amino carboxylic acids were successfully incorporated into the N-terminus of streptavidin by adding TAMRA-acylated initiator tRNAs to an E. coli cell-free translation system, although the incorporation efficiency differed depending on the amino carboxylic acid chain length. Based on this observation, 3-aminopropionic acid derivatives labeled with BODIPY, rhodamine, and cyanine fluorophores were designed and synthesized. The fluorescent-labeled 3-aminopropionic acid derivatives developed using BODIPY and rhodamine dyes could be incorporated with good efficiency. On the other hand, 6-aminohexanoic acid was effectively incorporated when labeled with cyanine dyes. The present study demonstrates that translation initiation can accept a wide variety of non-natural substrates and provides a useful method for N-terminal-specific labeling of proteins with various fluorophores.
- Miura, Masanori,Muranaka, Norihito,Abe, Ryoji,Hohsaka, Takahiro
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experimental part
p. 546 - 553
(2010/08/21)
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- Module assembly for protein-surface recognition: Geranylgeranyltransferase I bivalent inhibitors for simultaneous targeting of interior and exterior protein surfaces
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Synthetic chemical probes designed to simultaneously targeting multiple sites of protein surfaces are of interest owing to their potential application as site specific modulators of protein-protein interactions. A new approach toward bivalent inhibitors of mammalian type I geranylgeranyltransferase (GGTase I) based on module assembly for simultaneous recognition of both interior and exterior protein surfaces is reported. The inhibitors synthesized in this study consist of two modules linked by an alkyl spacer; one is the tetrapeptide CVIL module for binding to the interior protein surface (active pocket) and the other is a 3,4,5-alkoxy substituted benzoyl motif that contains three aminoalkyl groups designed to bind to the negatively charged protein exterior surface near the active site. The compounds were screened by two distinct enzyme inhibition assays based on fluorescence spectroscopy and incorporation of a [ 3H]-labeled prenyl group onto a protein substrate. The bivalent inhibitors block GGTase I enzymatic activity with Ki values in the submicromolar range and are approximately one order of magnitude and more than 150 times more effective than the tetrapeptide CVIL and the methyl benzoate derivatives, respectively. The bivalent compounds 6 and 8 were shown to be competitive inhibitors, suggesting that the CVIL module anchors the whole molecule to the GGTase I active site and delivers the other module to the targeting protein surface. Thus, our module-assembly approach resulted in simultaneous multiple-site recognition, and as a consequence, synergetic inhibition of GGTase I activity, thereby providing a new approach in designing protein-surface-directed inhibitors for targeting protein-protein interactions.
- Machida, Shinnosuke,Usuba, Kakeru,Blaskovich, Michelle A.,Yano, Akiko,Harada, Kazuo,Sebti, Said M.,Kato, Nobuo,Ohkanda, Junko
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supporting information; experimental part
p. 1392 - 1401
(2009/04/07)
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- Bolaamphiphiles promote phospholipid translocation across vesicle membranes
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A series of membrane-spanning bolaamphiphiles (molecules with two hydrophilic end groups connected by a hydrophobic linker) were prepared by a modular synthetic method and evaluated for their abilities to affect the dynamics of a surrounding bilayer membr
- Forbes, Christopher C.,DiVittorio, Kristy M.,Smith, Bradley D.
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p. 9211 - 9218
(2007/10/03)
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- Molecular tripods showing fluorescence enhancement upon binding to streptavidin
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(Chemical Equation Presented) We introduce a new approach to biotin-streptavidin assays based on a molecular tripod which consists of biotin, a fluorophore, and a quencher. The interaction between streptavidin and molecular tripods perturbs the ground-state quencher-fluorophore dimeric conformation in the absence of streptavidin and diminishes the intrinsic self-quenching of a quencher-fluorophore pair. The emission intensity of the molecular tripods plus streptavidin is 3.5-5.2 times that of molecular tripods in the absence of streptavidin.
- Tae, Woo Kim,Hey, Young Yoon,Park, Jung-Hyun,Kwon, Oh-Hoon,Jang, Du-Jeon,Hong, Jong-In
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p. 111 - 114
(2007/10/03)
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- Structural requirements of dictyopyrones isolated from Dictyostelium spp. in the regulation of Dictyostelium development and in anti-leukemic activity
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Cellular slime molds are fascinating to the field of developmental biology, and have long been used as excellent model organisms for the study of various aspects of multicellular development. We have recently isolated α-pyronoids, named dictyopyrones A-D (1-4), from various species of Dictyostelium cellular slime molds, and it was shown that compound 3 may regulate Dictyostelium development. In this study, we synthesized dictyopyrones A-D (1-4) and their analogues, investigated the physiological role of the molecules in cell growth and morphogenesis in D. discoideum, and further verified their effects on human leukemia K562 cells. Nitrogen-containing compounds 22 and 37 strongly inhibited cell growth in K562 leukemia cells, indicating that these compounds may be utilized as novel lead compounds for anti-leukemic agents.
- Kikuchi, Haruhisa,Sasaki, Kazunori,Sekiya, Jun'ichi,Maeda, Yasuo,Amagai, Aiko,Kubohara, Yuzuru,Oshima, Yoshiteru
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p. 3203 - 3214
(2007/10/03)
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- Design, synthesis, and pharmacological evaluation of thapsigargin analogues for targeting apoptosis to prostatic cancer cells
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A series of thapsigargin (TG) analogues, containing an amino acid applicable for conjugation to a peptide specifically cleaved by prostate-specific antigen (PSA), has been prepared to develop the drug-moiety of prodrugs for treatment of prostatic cancer. The analogues were synthesized by converting TG into O-8-debutanoylthapsigargin (DBTG) and esterifying O-8 of DBTG with various amino acid linkers. The compounds were evaluated for their ability to elevate the cytosolic Ca2+ concentration ([Ca2+]i) in TSU-Pr1 cells, their ability to inhibit the rabbit skeletal muscle SERCA pump, and their ability to induce apoptosis in TSU-Pr1 human prostatic cancer cells. The activity of analogues, in which DBTG were esterified with ω-amino acids [HOOC(CH2)nNH2, n = 5-7, 10, 11], increased with the linker length. Analogues with 3-[4-(L-leucinoylamino)phenyl]propanoyl, 6-(L-leucinoylamino)hexanoyl, and 12-(L -serinoylamino)dodecanoyl were considerably less active than TG, and analogues with 12-(L-alaninoylamino)dodecanoyl and 12-(L-phenylalaninoylamino)dodecanoyl were almost as active as TG. The 12-(L-leucinoylamino)dodecanoyl gave an analogue equipotent with TG, making this compound promising as the drug-moiety of a PSA sensitive prodrug of TG.
- Jakobsen,Denmeade,Isaacs,Gady,Olsen,Christensen
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p. 4696 - 4703
(2007/10/03)
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- Synthesis of medium ring lactams via cyclization reactions using polymer bound HOBT as catalyst
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The synthesis of medium ring lactams (7-, 9-, 11- and 13-membered rings) via cyclization reactions mediated by polymer bound 1-hydroxybenzotriazole (HOBT) is reported.
- Huang,Wei, Huang,Kalivretenos,Kalivretenos, Aristotle G.
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p. 9113 - 9116
(2007/10/02)
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