- Development of chemically stable solid phases for the target isolation with reduced nonspecific binding proteins
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Poly(methacrylate) matrices for affinity resins were designed and synthesized based on our previous results that nonspecific protein absorption on affinity resins strongly depended on their hydrophobic property. The novel affinity resins bearing FK506 (6a, 6b) captured specific binding protein, FKBP12, with a small amount of nonspecific binding proteins. The amount of nonspecific binding proteins on 6a-6b was much reduced compared to that on commercially available poly(methacrylate) resins, Toyopearl (8), and was almost the same as that on one of the most popular resins, Affigel (9). Interestingly, 6a and 6b could isolate FKBP52 as a specific binding protein as well, although 8 and 9 could not.
- Takahashi, Teruki,Shiyama, Takaaki,Hosoya, Ken,Tanaka, Akito
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Read Online
- Aromatically functionalized pseudo-crown ethers with unusual solvent response and enhanced binding properties
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Conformational flexibility in the host's structure is often considered detrimental to its binding. Flexible pseudo-crown ethers with aromatic donor/acceptor groups at the chain ends, however, displayed enhanced binding affinity and selectivity, particularly when the direct binding interactions were compromised by unfavorable solvents.
- Xing, Xiaoyu,Zhao, Yan
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Read Online
- Self-adhesion among phospholipid vesicles
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A compound was synthesized that binds to a phospholipid bilayer via a hydrophobic steroid thereby projecting a strong multi-hydrogen bonding unit into the surrounding water. As shown by light scattering, light microscopy, and cryo-HRSEM, this latter unit self-adheres and induces membrane-membrane attachments, as found in many biological systems. Copyright
- Menger,Zhang, Hailing
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Read Online
- THERAPEUTIC COMPOSITION OF CURE-PRO COMPOUNDS FOR TARGETED DEGRADATION OF BET DOMAIN PROTEINS, AND METHODS OF MAKING AND USAGE
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The present application is directed to a therapeutic composition, comprising two precursor compounds (monomers) that are suitable for assembly via two or more reversible covalent bonds. The monomers are polyfunctionalized molecules comprising a bioorthogo
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Paragraph 0339; 0476
(2022/02/15)
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- THERAPEUTIC CURE-PRO COMPOUNDS FOR TARGETED DEGRADATION OF BET DOMAIN PROTEINS, AND METHODS OF MAKING AND USING THEM
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The present application is directed to a therapeutically useful compound, comprised of two monomers that are linked to each other through two or more reversible covalent bonds. Each monomer is a polyfunctionalized molecule comprising a bioorthogonal linker element and ligand or pharmacophore, wherein the linker and ligand/pharmacophore are covalently coupled to each other either directly or through an optional connector moiety.
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Paragraph 0325; 0459; 0462
(2022/02/15)
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- Supramolecular compound nano-carrier as well as preparation method and application thereof
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The invention discloses a supramolecular compound nano-carrier as well as a preparation method and application thereof, and relates to the technical field of polymer chemistry and biological detection engineering. According to the supramolecular compound nano-carrier disclosed by the invention, a two-dimensional nanosheet supramolecular structure system generated by self-assembly is driven by an anion induction effect, and a supramolecular compound nano-carrier is of a single-layer nanosheet supramolecular structure constructed by a highly-oriented one-dimensional nanorod. A hydrophobic perylene group part is used as a skeleton part for constructing the highly-oriented one-dimensional nanorod, and the charge density of a single-layer nanosheet can be regulated and controlled. The surface of the water-soluble multivalent hydrophilic part can be loaded with DNAzyme deoxyribozyme for specific detection of heavy metal ions through electrostatic interaction, and the water-soluble multivalent supramolecular compound nano sensor is constructed. Based on a fluorescence change mechanism caused by specific cutting of heavy metal ions, The fluorescence detection of the heavy metal ions in food and biological tissues is realized, and the detection effect of the heavy metal ions is greatly enhanced.
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Paragraph 0109; 0125
(2021/08/14)
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- PROTAC compound for targeted degradation of IDO1, and preparation method and application thereof
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The invention provides a PROTAC compound represented by formula I and used for targeted degradation of IDO1, and a pharmaceutically acceptable salt, a hydrate or a solvate thereof. In the formula I, Xrepresents -CH2 or -C = O, Y represents -CH2 or -C= O, and n is a natural number from 2 to 9. The PROTAC compound for targeted degradation of the IDO1 has efficient activity of targeted degradation of the IDO1 protein.
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Paragraph 0024-0026; 0046-0049
(2020/06/17)
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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 2254; 2257
(2019/07/10)
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- EXENATIDE MODIFIER AND USE THEREOF
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Disclosed are an exenatide modifier for connecting the exenatide to a fatty chain with a carboxy in the terminus thereof by means of a hydrophilic connecting arm, and a use thereof in preparing drugs serving as a GLP-1 receptor agonist; a use in preparing drugs for preventing and/or treating diseases and/or symptoms associated with a low GLP-1 receptor activity; a use in preparing drugs for diseases and/or symptoms associated with glycometabolism; a use in preparing drugs for diabetes; a use in preparing drugs for fatty liver disease, and a use in preparing drugs for losing weight.
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Paragraph 0102
(2018/05/24)
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- Ligand-Phospholipid Conjugation: A Versatile Strategy for Developing Long-Acting Ligands That Bind to Membrane Proteins by Restricting the Subcellular Localization of the Ligand
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We hypothesized that if drug localization can be restricted to a particular subcellular domain where their target proteins reside, the drugs could bind to their target proteins without being metabolized and/or excreted, which would significantly extend the half-life of the corresponding drug-target complex. Thus, we designed ligand-phospholipid conjugates in which the ligand is conjugated with a phospholipid through a polyethylene glycol linker to restrict the subcellular localization of the ligand in the vicinity of the lipid bilayer. Here, we present the design, synthesis, pharmacological activity, and binding mode analysis of ligand-phospholipid conjugates with muscarinic acetylcholine receptors as the target proteins. These results demonstrate that ligand-phospholipid conjugation can be a versatile strategy for developing long-acting ligands that bind to membrane proteins in drug discovery.
- Kawamura, Shuhei,Ito, Yoshihiko,Hirokawa, Takatsugu,Hikiyama, Eriko,Yamada, Shizuo,Shuto, Satoshi
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supporting information
p. 4020 - 4029
(2018/05/07)
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- CONJUGATES COMPRISING SELF-IMMOLATIVE GROUPS AND METHODS RELATED THERETO
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In some aspects, the invention relates to an antibody-drug conjugate, comprising an antibody; a linker; and an active agent. The antibody-drug conjugate may comprise a self- immolative group. The linker may comprise an O-substituted oxime, e.g., wherein the oxygen atom of the oxime is substituted with a group that covalently links the oxime to the active agent; and the carbon atom of the oxime is substituted with a group that covalently links the oxime to the antibody.
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Page/Page column 106; 107
(2017/06/27)
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- CONJUGATES COMPRISING PEPTIDE GROUPS AND METHODS RELATED THERETO
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In some aspects, the invention relates to an antibody-drug conjugate, comprising an antibody; a linker; and at least two active agents. In preferred embodiments, the linker comprises a peptide sequence of a plurality of amino acids, and at least two of the active agents are covalently coupled to side chains of the amino acids. The antibody-drug conjugate may comprise a self-immolative group, preferably two-self-immolative groups. The linker may comprise an O-substituted oxime, e.g., wherein the oxygen atom of the oxime is substituted with a group that covalently links the oxime to the active agent; and the carbon atom of the oxime is substituted with a group that covalently links the oxime to the antibody.
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Page/Page column 117
(2017/08/08)
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- Solid-Phase-Based Synthesis of Ureidopyrimidinone-Peptide Conjugates for Supramolecular Biomaterials
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Supramolecular polymers have shown to be powerful scaffolds for tissue engineering applications. Supramolecular biomaterials functionalized with ureidopyrimidinone (UPy) moieties, which dimerize via quadruple hydrogen-bond formation, are eminently suitable for this purpose. The conjugation of the UPy moiety to biologically active peptides ensures adequate integration into the supramolecular UPy polymer matrix. The structural complexity of UPy-peptide conjugates makes their synthesis challenging and until recently low yielding, thus restricted the access to structurally diverse derivatives. Here we report optimization studies of a convergent solid-phase based synthesis of UPy-modified peptides. The peptide moiety is synthesized using standard Fmoc solid-phase synthesis and the UPy fragment is introduced on the solid-phase simplifying the synthesis and purification of the final UPy-peptide conjugate. The convergent nature of the synthesis reduces the number of synthetic steps in the longest linear sequence compared to other synthetic approaches. We demonstrate the utility of the optimized route by synthesizing a diverse range of biologically active UPy-peptide bioconjugates in multimilligram scale for diverse biomaterial applications. 1 Introduction 2 Divergent Synthesis 3 Convergent Synthesis 4 UPy-Amine Strategy 5 UPy-Carboxylic Acid Strategy 6 Conclusion.
- De Feijter, Isja,Goor, Olga J. G. M.,Hendrikse, Simone I. S.,Comellas-Aragonès, Marta,S?ntjens, Serge H. M.,Zaccaria, Sabrina,Fransen, Peter P. K. H.,Peeters, Joris W.,Milroy, Lech-Gustav,Dankers, Patricia Y. W.
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supporting information
p. 2707 - 2713
(2015/11/27)
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- Improvement of solid material for affinity resins by application of long PEG spacers to capture the whole target complex of FK506
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Solid materials for affinity resins bearing long PEG spacers between a functional group used for immobilization of a bio-active compound and the solid surface were synthesized to capture not only small target proteins but also large and/or complex target proteins. Solid materials with PEG1000 or PEG2000 as spacers, which bear a benzenesulfonamide derivative, exhibited excellent selectivity between the specific binding protein carbonic anhydrase type II (CAII) and non-specific ones. These materials also exhibited efficacy in capturing a particular target at a maximal amount. Affinity resins using solid materials with PEG1000 or PEG2000 spacers, bear a FK506 derivative, successfully captured the whole target complex of specific binding proteins at the silver staining level, while all previously known affinity resins with solid materials failed to achieve this objective. These novel affinity resins captured other specific binding proteins such as dynamin and neurocalcin δ as well.
- Mabuchi, Miyuki,Shimizu, Tadashi,Ueda, Masahiro,Mitamura, Kuniko,Ikegawa, Shigeo,Tanaka, Akito
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p. 2788 - 2792
(2015/06/08)
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- Identifying novel targets in renal cell carcinoma: Design and synthesis of affinity chromatography reagents
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Two novel scaffolds, 4-pyridylanilinothiazoles (PAT) and 3-pyridylphenylsulfonyl benzamides (PPB), previously identified as selective cytotoxins for von Hippel-Lindau-deficient Renal Carcinoma cells, were used as templates to prepare affinity chromatograp
- Bonnet, Muriel,Flanagan, Jack U.,Chan, Denise A.,Giaccia, Amato J.,Hay, Michael P.
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p. 711 - 720
(2014/01/23)
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- Solid phase synthesis of functionalised SAM-forming alkanethiol- oligoethyleneglycols
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We present an efficient solid phase synthesis methodology that provides easy access to a range of functionalised long-chain alkanethiol- oligoethyleneglycols that form well-defined self-assembled monolayers on gold and are compatible with pre- or post-ass
- Murray, James,Nowak, Dominika,Pukenas, Laurynas,Azhar, Rizuan,Guillorit, Mathieu,Waelti, Christoph,Critchley, Kevin,Johnson, Steven,Bon, Robin S.
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p. 3741 - 3744
(2014/06/10)
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- SUBSTITUTED BENZAMIDES AND THEIR USES
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Provided herein are Substituted Benzamides, compositions, and method of their manufacture and use.
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Page/Page column 112-113
(2013/11/05)
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- Unmasking photolithography: A versatile way to site-selectively pattern gold substrates
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Surface chemistry: A new method for creating complex patterns on gold substrates is reported. Substrates were functionalized with nitroveratryl- protected carboxylic acid and hydroxy-terminated thiol monomers and patterned with a direct-write photolithography system to produce complex functional group gradients. In addition, two amine molecules were sequentially coupled on the substrate under spatial control (see picture). Copyright
- Hynes, Matthew J.,Maurer, Joshua A.
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supporting information; experimental part
p. 2151 - 2154
(2012/04/05)
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- BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS
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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 ARM-H′ function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and b
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Page/Page column 37
(2012/11/07)
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- Protein assembly along a supramolecular wire
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Discotic molecules self-assemble into supramolecular wires that act as platforms for directed protein assembly via appended biotin functionalities.
- Mueller, Marion K.,Petkau, Katja,Brunsveld, Luc
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supporting information; experimental part
p. 310 - 312
(2011/03/17)
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- Supramolecular gelation of alcohol and water by synthetic amphiphilic gallic acid derivatives
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The supramolecular organogelation of alcohols was observed in relatively hydrophobic amphiphiles with a short oligo(ethylene glycol) unit and three long alkyl chains at room temperature, while the hydrogelation occurred in more hydrophilic gelators with a longer poly(ethylene glycol) unit and two long alkyl chains at various temperatures. When a hot aqueous solution of some of the synthetic hydrogelators was cooled down, the supramolecular hydrogel was formed at room temperature. In some other amphiphiles with less intermolecular interactivity in water at room temperature, a reverse phase transition of sol to gel was observed by elevating the temperature of their aqueous systems, especially below a physiological temperature, 37 °C. The supramolecular hydrogelation at a low or high temperature was dependent on a slight molecular modification of the synthetic amphiphiles.
- Tamiaki, Hitoshi,Ogawa, Keishiro,Enomoto, Keisuke,Taki, Kazutaka,Hotta, Atsushi,Toma, Kazunori
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supporting information; experimental part
p. 1661 - 1666
(2010/04/24)
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- Synthesis and biological evaluation of functionalised tetrahydro-β- carboline analogues as inhibitors of Toxoplasma gondii invasion
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Techniques for the identification of the protein target(s) of small molecules are proving very important following an increase in the use of phenotype-based screening in chemical biology and drug discovery. One approach, known as the yeast-3-hybrid approach, has shown considerable potential. A key factor in the success of this approach is the preparation of a complex molecule referred to as a chemical inducer of dimerisation (CID). The synthesis of two CIDs based on a bioactive tetrahydro-β-carboline core structure is reported and evidence presented that shows the CIDs are of utility in this approach. A series of chemo- and bioinformatic studies coupled with SAR development inspired the choice of CIDs.
- Walton, Jeffrey G. A.,Patterson, Stephen,Liu, Gu,Haraldsen, Jeralyn D.,Hollick, Jonathan J.,Slawin, Alexandra M. Z.,Ward, Gary E.,Westwood, Nicholas J.
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scheme or table
p. 3049 - 3060
(2011/02/25)
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- Therapeutic and diagnostic ligand systems comprising transport molecule binding properties and medicaments containing the same
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The invention relates to transport molecule binding ligand compounds which comprise a therapeutically and/or diagnostically active substance and a carrier molecule-affine substance with a high association constant to the carrier molecule. The invention also relates to medicaments containing these ligand compounds and to diagnostic kits.
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- Synthesis of a series of oligo(ethylene glycol)-terminated alkanethiol amides designed to address structure and stability of biosensing interfaces
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A strategy for the synthesis of a series of closely related oligo(ethylene glycol)-terminated alkanethiol amides (principally HS(CH2)mCONH(CH2CH2O) nH; m = 2, 5, 11, 15, n = 1, 2, 4, 6, 8, 10, 12) and analogous esters has been developed. These compounds were made to study the structure and stability of self-assembled monolayers (SAMs) on gold in the prospect of designing new biosensing interfaces. For this purpose, monodisperse heterofunctional oligo(ethylene glycols) with up to 12 units were prepared. Selective monoacylation of the symmetrical tetra- and hexa(ethylene glycol) diols as their mesylates with the use of silver(I) oxide was performed. The synthetic approach was based on carbodiimide couplings of various oligo(ethylene glycol) derivatives to ω-(acetylthio) carboxylic acids via a terminal amino or hydroxyl function. SAM structures on gold were studied with respect to thickness, wettability (water contact angles ~30°), and conformation. A good fit was obtained for the relation between monolayer thickness (d) and the number of units in the oligo(ethylene glycol) chain (n): d = 2.8n + 21.8 (A). Interestingly, the corresponding infrared spectroscopy analysis showed a dramatic change in conformation of the oligomeric chains from all-trans (n = 4) to helical (n ≥ 6) conformation. A crystalline helical structure was observed in the SAMs for n > 6.
- Svedhem,Hollander,Shi,Konradsson,Liedberg,Svensson
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p. 4494 - 4503
(2007/10/03)
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- Synthesis and conformational characterization of tethered, self-complexing 1,5-dialkoxynaphthalene/1,4,5,8-naphthalenetetracarboxylic diimide systems
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Chemists are beginning to explore the abiotic folding of synthetic chains, and the term "foldamers" has been used to characterize oligomers with a strong inclination to adopt specific, compact conformations. The characterization of folded structure in solution is one of the difficult challenges facing the foldamer field. Aedamers were the first foldamers to make use of aromatic-aromatic interactions in water to direct folding and were designed to have several spectroscopic handles with which to probe folding conformations in solution. Herein is reported the synthesis and spectroscopic characterization of eleven aedamer dimers, with linkers chosen to provide a spectrum of lengths and flexibilities. The dimers, composed of one electron rich (1,5-dialkoxynaphthalene) and one electron deficient (1,4,5,8-naphthalenetetracarboxylic diimide) aromatic group tethered by a linker, are the smallest aedamer folding unit. The powerful spectroscopic handles associated with the stacked aedamer groups were exploited in a comprehensive spectroscopic analysis of conformation that included UV-vis absorption spectroscopy, fluorescence measurements (including time-resolved studies), as well as detailed NMR studies. The spectra were interpreted in the context of molecular modeling/spectral prediction and structural models were developed for the different dimers in aqueous solution. In most instances, the observed data was best described by an ensemble of predicted structures as opposed to one or few conformers. Thus, in the case of these aedamer dimers, "folding" does not appear to imply a two-state model with a rigid, unique conformation. Rather, the reported analysis indicates the data can best be described by a more dynamic model in which a given molecule spends its time in different folded conformations that are related by having a characteristic face-to-face stacking arrangement of the aromatic units.
- Zych, Andrew J.,Iverson, Brent L.
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p. 8898 - 8909
(2007/10/03)
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- Synthesis of heparin-like antithrombotics having perphosphorylated thrombin binding domains
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The synthesis of three heparin analogues (i.e. compounds VI-VIII) having perphosphorylated thrombin binding domains (TBDs) is reported. These compounds were tested in vitro for their antithrombin III (ATIII)-mediated anti-Xa and antithrombin activities. Conjugates VI and VIII show a remarkable increase in antithrombin activity compared to the structurally related conjugates with persulfated TBDs (i.e. compounds IV and V), whereas compound VII displays a diminished activity.
- Buijsman, Rogier C.,Basten, Jan E. M.,Dreef-Tromp, Cornelia M.,Van Der Marel, Gijsbert A.,Van Boeckel, Constant A. A.,Van Boom, Jacques H.
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p. 1881 - 1890
(2007/10/03)
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- REDUCTION D'AZIDES EN AMINES PAR LE FORMIATE D'AMMONIUM PAR "TRANSFERT D'HYDROGENE CATALYSE" (CTH)
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The azides are reduced to amines in very good yields by "Catalytic Transfer Hydrogenation" (CTH) using ammonium formate.
- Gartiser, T.,Selve, C.,Delpuech, J.-J.
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p. 1609 - 1610
(2007/10/02)
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