- THERAPEUTIC CURE-PRO COMPOUNDS FOR TARGETED DEGRADATION OF BET DOMAIN PROTEINS, AND METHODS OF MAKING AND USING THEM
-
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.
- -
-
Paragraph 0325; 0459; 0461
(2022/02/15)
-
- THERAPEUTIC COMPOSITION OF CURE-PRO COMPOUNDS FOR TARGETED DEGRADATION OF BET DOMAIN PROTEINS, AND METHODS OF MAKING AND USAGE
-
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
- -
-
Paragraph 0339; 0475
(2022/02/15)
-
- Design, synthesis and activity study of a novel PI3K degradation by hijacking VHL E3 ubiquitin ligase
-
PI3K kinase plays an important role in regulating key processes in cells, such as cell growth, metabolism, proliferation, and apoptosis. The overexpression of PI3K kinase exists in many cancers. The proteolytic target chimera (PROTAC) technology is a new technology that uses the ubiquitin–proteasome system to degrade a given target protein. It has been described that CRBN-based PROTAC targets the degradation of PI3K kinase. However, PROTAC based on VHL has not been reported yet. Here, we connected the previously obtained highly active PI3K inhibitor to the VHL ligand through different small molecules, and obtained a series of PROTAC molecules targeting PI3K kinase. Obtain the most active compound through screening. It provides evidence for the feasibility of PROTAC technology to recruit VHL E3 ligase in PI3K kinase.
- Li, Chuchu,Liu, Xiaoqing,Ma, Mingliang,Wang, Haili
-
-
- ANTIBODY-DRUG CONJUGATES COMPRISING ANTI-B7-H3 ANTIBODIES
-
The present disclosure relates to antibody-drug conjugates (ADCs) wherein one or more active agents are conjugated to an anti-B7-H3 antibody through a linker. The linker may comprise a unit that covalently links active agents to the antibody. The disclosure further relates to monoclonal antibodies and antigen binding fragments, variants, multimeric versions, or bispecifics thereof that specifically bind B7-H3, as well as methods of making and using these anti-B7-H3 antibodies and antigen-binding fragments thereof in a variety of therapeutic, diagnostic and prophylactic indications
- -
-
Page/Page column 106; 109-110; 119
(2022/01/04)
-
- Supramolecular compound nano-carrier as well as preparation method and application thereof
-
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.
- -
-
Paragraph 0109; 0124
(2021/08/14)
-
- COMPOSITIONS AND METHODS RELATED TO MOLECULAR CONJUGATION
-
The invention relates to activated Michael acceptor (AMA) compounds that can undergo conjugation with biomolecules containing Michael donor moieties, thereby providing plasma-stable antibody-drug conjugates (ADCs). Pharmaceutical compositions of the ADCs are disclosed as well. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.
- -
-
Page/Page column 49; 50
(2021/06/11)
-
- PROTAC compound for targeted degradation of IDO1, and preparation method and application thereof
-
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.
- -
-
Paragraph 0024-0026; 0044-0045
(2020/06/17)
-
- Synthesis of branched monodisperse oligoethylene glycols and 19f mri-traceable biomaterials through reductive dimerization of azides
-
Multifunctionalized and branched M-OEGs represent valuable PEGylation agents, linkers, and scaffolds in biomedicine. However, the tedious synthesis limited their availability and application. We herein present an azide reductive dimerization method for the convenient synthesis of aza-M-OEGs and derivatives, which provides easy access to a variety of multifunctionalized and branched M-OEGs in one step. With this method, hexa-arm M-OEGs with 54 symmetrical fluorines were synthesized in two steps as a water-soluble, self-assemble, 19F MRI sensitive, and biocompatible dendritic biomaterial.
- Chen, Shizhen,Jiang, Zhong-Xing,Li, Yu,Yang, Hao,Yang, Zhigang,Yuan, Yuan,Zhang, Huaibin,Zhang, Jing,Zhou, Xin
-
p. 6778 - 6787
(2020/06/08)
-
- A synthetic 2,3-diarylindole induces microtubule destabilization and G2/M cell cycle arrest in lung cancer cells
-
The anticancer potential of a synthetic 2,3-diarylindole (PCNT13) has been demonstrated in A549 lung cancer cells by inducing both apoptosis and autophagic cell death. In this report, we designed to connect a fluorophore to the compound via a hydrophilic linker for monitoring intracellular localization. The best position for linker attachment was identified from cytotoxicity and effect on cell morphology of newly synthesized PCNT13 derivatives bearing hydrophilic linker. Cytotoxicity and effect on cell morphology related to the parental compound were used to identify the optimum position for linker attachment in the PCNT13 chemical structure. The fluorophore-PCNT13 conjugate was found to localize in the cytoplasm. Microtubules were found to be one of the cytosolic target proteins of PCNT13, as the compound could inhibit tubulin polymerization in vitro. A molecular docking study revealed that PCNT13 binds at the colchicine binding site on the α/β-tubulin heterodimer. The effect of PCNT13 on microtubule dynamics caused cell cycle arrest in the G2/M phase as analyzed by flow cytometric analysis.
- Thanaussavadate, Bongkotrat,Ngiwsara, Lukana,Lirdprapamongkol, Kriengsak,Svasti, Jisnuson,Chuawong, Pitak
-
-
- Targeting G Protein-Coupled Receptors with Magnetic Carbon Nanotubes: The Case of the A3 Adenosine Receptor
-
The A3 adenosine receptor (AR) is a G protein-coupled receptor (GPCR) overexpressed in the membrane of specific cancer cells. Thus, the development of nanosystems targeting this receptor could be a strategy to both treat and diagnose cancer. Iron-filled carbon nanotubes (CNTs) are an optimal platform for theranostic purposes, and the use of a magnetic field can be exploited for cancer magnetic cell sorting and thermal therapy. In this work, we have conjugated an A3AR ligand on the surface of iron-filled CNTs with the aim of targeting cells overexpressing A3ARs. In particular, two conjugates bearing PEG linkers of different length were designed. A docking analysis of A3AR showed that neither CNT nor linker interferes with ligand binding to the receptor; this was confirmed by in vitro preliminary radioligand competition assays on A3AR. Encouraged by this result, magnetic cell sorting was applied to a mixture of cells overexpressing or not the A3AR in which our compound displayed indiscriminate binding to all cells. Despite this, it is the first time that a GPCR ligand has been anchored to a magnetic nanosystem, thus it opens the door to new applications for cancer treatment.
- Pineux, Florent,Federico, Stephanie,Klotz, Karl-Norbert,Kachler, Sonja,Michiels, Carine,Sturlese, Mattia,Prato, Maurizio,Spalluto, Giampiero,Moro, Stefano,Bonifazi, Davide
-
p. 1909 - 1920
(2020/09/11)
-
- COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF
-
Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.
- -
-
Page/Page column 169-170
(2020/07/21)
-
- COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF
-
Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a -S(=0)(=N-)- functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.
- -
-
Page/Page column 160-161
(2020/09/03)
-
- FUSED HETEROCYCLIC BENZODIAZEPINE DERIVATIVES AND USES THEREOF
-
The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.
- -
-
Page/Page column 126-127
(2020/05/29)
-
- COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF
-
Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.
- -
-
Page/Page column 169
(2019/01/21)
-
- NOVEL BENZODIAZEPINE DERIVATIVES AND USES THEREOF
-
The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.
- -
-
Paragraph 0522-0524
(2019/12/24)
-
- IRAK DEGRADERS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same.
- -
-
Paragraph 2254; 2256
(2019/07/10)
-
- Radioiodinated progesterone derivative for progesterone receptor targeting with enhanced nucleus uptake via phenylboronic acid conjugation
-
A novel 131I-radiolabeled probe with aromatic boronate motif (131I-EIPBA) was designed to target progesterone receptor (PR)–positive breast cancer with enhanced nucleus uptake. Acetylene progesterone was conjugated with pegylated phe
- Gao, Fei,Peng, Chenyu,Li, Jindian,Zhuang, Rongqiang,Guo, Zhide,Xu, Duo,Su, Xinhui,Zhang, Xianzhong
-
p. 301 - 309
(2019/06/21)
-
- Medicine conjugate and method for prolonging half-life of medicine molecule
-
The invention discloses a medicine conjugate and a method for prolonging half-life of a medicine molecule. The medicine conjugate is prepared through modifying the medicine molecule with a micromolecule combined with a half antigen, wherein the half antigen is the half antigen having an endogenous antibody. The half antigen molecule is modified on the medicine molecule, and the modified medicine molecule can be specifically combined with the endogenous antibody in accordance with the half antigen, so that the in vivo half-life of the medicine molecule can be notably prolonged.
- -
-
Paragraph 0061-0064; 0081-0084
(2019/11/19)
-
- Expedient synthesis of trifunctional oligoethyleneglycol-amine linkers and their use in the preparation of PEG-based branched platforms
-
We designed a convergent synthesis pathway that provides access to trifunctional oligoethyleneglycol-amine (OEG-amine) linkers. By applying the reductive coupling of a primary azide to bifunctional OEG-azide precursors, the corresponding symmetrical dialkylamine bearing two homo-functional end chain groups and a central nitrogen was obtained. These building blocks bear minimal structural perturbation compared to the native OEG backbone which makes them attractive for biomedical applications. The NMR investigations of the mechanism process reveal the formation of nitrile and imine intermediates which can react with the reduced free amine form. Additionally, these trifunctional OEG-amine linkers were employed in a coupling reaction to afford branched multifunctional PEG dendrons which are molecularly defined. These discrete PEG-based dendrons (n = 16, 18 and 36) could be useful for numerous applications where multivalency is required.
- Ursuegui, Sylvain,Schneider, Jérémy P.,Imbs, Claire,Lauvoisard, Florian,Dudek, Marta,Mosser, Michel,Wagner, Alain
-
supporting information
p. 8579 - 8584
(2019/01/07)
-
- BIFUNCTIONAL ANTIFUNGAL AGENTS AND METHODS OF TREATING FUNGAL INFECTION
-
The present invention is directed to bifunctional compounds which are useful in the treatment of fungal infections. The present compounds contains at least one fungal binding moiety (FBM) which is linked to at least one antibody binding moiety (ΑB/s
- -
-
Page/Page column 44, 47
(2018/03/09)
-
- HDAC INHIBITORS-BASED ANTIBODY DRUG CONJUGATES (ADCs) AND USE IN THERAPY
-
The present invention relates to novel Histone Deacetylase Inhibitors (HDACi)- based antibody drug conjugates particularly with antibodies directed to ErbB1, ErbB2 and ErbB3 receptors, pharmaceutical compositions comprising said antibodies as well as to their use in the treatment of cancer or tumor and other diseases where a modulation of one or more histone deacetylase isoforms can be effective for therapeutic interventions.
- -
-
Page/Page column 71; 72
(2018/10/25)
-
- EXENATIDE MODIFIER AND USE THEREOF
-
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.
- -
-
Paragraph 0101
(2018/05/24)
-
- Aromatically functionalized pseudo-crown ethers with unusual solvent response and enhanced binding properties
-
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
-
supporting information
p. 1627 - 1631
(2018/03/21)
-
- Neutralization of Pathogenic Fungi with Small-Molecule Immunotherapeutics
-
Systemic fungal infections represent an important public health concern, and new antifungal agents are highly desirable. Herein, we describe the design, synthesis, and biological evaluation of a novel class of antifungal compounds called antibody-recruiting molecules targeting fungi (ARM-Fs). Our approach relies on the use of non-peptidic small molecules, which selectively bind fungal cells and recruit endogenous antibodies to their surfaces, resulting in immune-mediated clearance. Using the opportunistic fungal pathogen Candida albicans as a model, we identified a highly specific bifunctional molecule able to mediate the engulfment and phagocytosis of C. albicans cells by human immune cells in biologically relevant functional assays. This work represents a novel therapeutic approach to treating fungal illness with significant potential to complement and/or combine with existing treatment strategies.
- Chirkin, Egor,Muthusamy, Viswanathan,Mann, Paul,Roemer, Terry,Nantermet, Philippe G.,Spiegel, David A.
-
supporting information
p. 13036 - 13040
(2017/09/18)
-
- CONJUGATES COMPRISING SELF-IMMOLATIVE GROUPS AND METHODS RELATED THERETO
-
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.
- -
-
Page/Page column 63; 64
(2017/06/27)
-
- CONJUGATES COMPRISING PEPTIDE GROUPS AND METHODS RELATED THERETO
-
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.
- -
-
Page/Page column 74; 75
(2017/08/08)
-
- Intracellular Protein-Labeling Probes for Multicolor Single-Molecule Imaging of Immune Receptor-Adaptor Molecular Dynamics
-
Single-molecule imaging (SMI) has been widely utilized to investigate biomolecular dynamics and protein-protein interactions in living cells. However, multicolor SMI of intracellular proteins is challenging because of high background signals and other lim
- Sato, Ryota,Kozuka, Jun,Ueda, Masahiro,Mishima, Reiko,Kumagai, Yutaro,Yoshimura, Akimasa,Minoshima, Masafumi,Mizukami, Shin,Kikuchi, Kazuya
-
supporting information
p. 17397 - 17404
(2017/12/15)
-
- LINKER MOLECULE FOR MULTIPLEX RECOGNITION BY ATOMIC FORCE MICROSCOPY (AFM)
-
Some of the embodiments of the present disclosure relate to a compound of the formula, and methods of preparing and using same.
- -
-
Paragraph 0023; 0026
(2017/06/12)
-
- SILICON BASED DRUG CONJUGATES AND METHODS OF USING SAME
-
Described herein are silicon based conjugates capable of delivering one or more payload moieties to a target cell or tissue. Contemplated conjugates may include a silicon-heteroatom core, one or more optional catalytic moieties, a targeting moiety that permits accumulation of the conjugate within a target cell or tissue, one or more payload moieties (e.g., a therapeutic agent or imaging agent), and two or more non-interfering moieties covalently bound to the silicon-heteroatom core.
- -
-
Paragraph 0702; 0721; 0722
(2017/08/07)
-
- SILANOL BASED THERAPEUTIC PAYLOADS
-
Described herein in part are silanol based therapeutic payloads comprising a silanol terminus, a divalent spacer moiety, and a drug moiety capable of effecting a target cell or tissue.
- -
-
Paragraph 00160
(2018/01/17)
-
- Compound used for measuring blood serum cholyglycine and preparation method for compound
-
The invention discloses a compound for measuring blood serum cholyglycine. The compound has a structure as shown in formula (A): seen in the description, wherein in the formula (A), n is 0 or a positive integer, R1 is selected from NH, O and S, R2 is selected from O, NH and CH2, and R3 is selected from a hydrophilic group, biotin or an immune protein carrier. The compound is beneficial for reducing the steric effect when cholyglycine is cross-linked with protein, increasing water solubility of cross-linked proteantigen at the same time, and is convenient for stimulating the immunity. The modified cholyglycine compound is used as an antibody for preparation of immunogen, and can be used for specifically distinguishing the cholyglycine and combining with the cholyglycine. The modified cholyglycine and the modified antibody can be used for establishing immunological detection methods such as immunological turbidimetry, competitive enzyme-linked immunosorbent assay and colloidal gold immunochromatography, so that accurate measurement on concentration level of cholyglycine in a specimen is realized.
- -
-
Paragraph 0050; 0055; 0056; 0057; 0058; 0059
(2017/07/21)
-
- Amide bond-containing monodisperse polyethylene glycols beyond 10000 da
-
Although monodisperse polyethylene glycols (M-PEGs) above 4000 Da are especially valuable in biomedical applications, their synthesis remains a long-standing challenge. To this end, a peptide-based strategy for such M-PEGs was developed. With macrocyclic sulfates as the key intermediates, a panel of oligoethylene glycol (OEG) containing ω-amino acids were prepared with high efficiency. Through solid phase peptide synthesis (SPPS), these amino acids were conveniently assembled into a series of amide bond-containing M-PEGs with high flexibility in molecular weight and amide density selection. With this strategy, an M-PEG of 10262 Da was prepared on a gram scale and its biocompatibility was assessed in a mice model.
- Wan, Zihong,Li, Yu,Bo, Shaowei,Gao, Ming,Wang, Xuemeng,Zeng, Kai,Tao, Xin,Li, Xuefei,Yang, Zhigang,Jiang, Zhong-Xing
-
p. 7912 - 7919
(2016/08/30)
-
- COMPOUNDS FOR THE MODULATION OF MYC ACTIVITY
-
The present invention provides novel compounds of Formula (I) and Formula (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases, e.g., cancers (e.g., breast cancer, prostate cancer, lymphoma, lung cancer, pancreatic cancer, ovarian cancer, neuroblastoma, or colorectal cancer), benign neoplasms, angio genesis, inflammatory diseases, fibrosis (e.g., polycystic kidney disease), autoinflammatory diseases, and autoimmune diseases in a subject.
- -
-
Paragraph 1063-1064
(2017/01/31)
-
- MACROCYCLIC PEPTIDES USEFUL AS IMMUNOMODULATORS
-
The present disclosure provides compounds which are immunomodulators and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.
- -
-
Page/Page column 472; 473
(2016/06/06)
-
- Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates
-
The use of nanotechnologies for biomedical applications took a real development during these last years. To allow an effective targeting for biomedical imaging applications, the adsorption of plasmatic proteins on the surface of nanoparticles must be prevented to reduce the hepatic capture and increase the plasmatic time life. In biologic media, metal oxide nanoparticles are not stable and must be coated by biocompatible organic ligands. The use of phosphonate ligands to modify the nanoparticle surface drew a lot of attention in the last years for the design of highly functional hybrid materials. Here, we report a methodology to synthesize bisphosphonates having functionalized PEG side chains with different lengths. The key step is a procedure developed in our laboratory to introduce the bisphosphonate from acyl chloride and tris(trimethylsilyl)phosphite in one step.
- Kachbi-Khelfallah, Souad,Monteil, Maelle,Cortes-Clerget, Margery,Migianu-Griffoni, Evelyne,Pirat, Jean-Luc,Gager, Olivier,Deschamp, Julia,Lecouvey, Marc
-
supporting information
p. 1366 - 1370
(2016/08/02)
-
- Solid-Phase-Based Synthesis of Ureidopyrimidinone-Peptide Conjugates for Supramolecular Biomaterials
-
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.
-
supporting information
p. 2707 - 2713
(2015/11/27)
-
- Alternative reagents for methotrexate as immobilizing anchor moieties in the optimization of MASPIT: Synthesis and biological evaluation
-
We report the evaluation of two alternative chemical dimerizer approaches aimed at increasing the sensitivity of MASPIT, a three-hybrid system that enables small-molecule target protein profiling in intact human cells. To circumvent the potential limitati
- De Clercq, Dries J.H.,Risseeuw, Martijn D.P.,Karalic, Izet,De Smet, Anne-Sophie,Defever, Dieter,Tavernier, Jan,Lievens, Sam,Van Calenbergh, Serge
-
p. 834 - 843
(2015/03/30)
-
- BCR-ABL TYROSINE-KINASE LIGANDS CAPABLE OF DIMERIZING IN AN AQUEOUS SOLUTION, AND METHODS OF USING SAME
-
Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. invivo) to form a multimer (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding sites on a Bcr-Abl tyrosine kinase.
- -
-
Paragraph 00461; 00476; 00477; 00549; 00564; 00565
(2015/07/23)
-
- SUBSTITUTED BENZAMIDES AND THEIR USES
-
Provided herein are Substituted Benzamides, compositions, and method of their manufacture and use.
- -
-
Paragraph 0578
(2015/12/01)
-
- Heteroarylacetic phenylbenzamide, composition and method of use (by machine translation)
-
Provided are certain heteroaryl benzamides, compositions, and methods of their manufacture and use.
- -
-
Paragraph 0289
(2016/10/08)
-
- Solid phase synthesis of functionalised SAM-forming alkanethiol- oligoethyleneglycols
-
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.
-
p. 3741 - 3744
(2014/06/10)
-
- Identifying novel targets in renal cell carcinoma: Design and synthesis of affinity chromatography reagents
-
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.
-
p. 711 - 720
(2014/01/23)
-
- An easy access to asymmetrically substituted oligoethylene glycols from 18-crown-6
-
A new route for the preparation of multi-gram quantities of the heterobifunctional oligoethylene glycol (OEG) derivatives (n = 6, 7) is reported based on decyclization of 18-crown-6.
- Abronina, Polina I.,Zinin, Alexander I.,Orlova, Anna V.,Sedinkin, Sergey L.,Kononov, Leonid O.
-
p. 4533 - 4535
(2013/08/23)
-
- Extension into the entrance channel of HIV-1 reverse transcriptase - Crystallography and enhanced solubility
-
Non-nucleoside inhibitors of HIV-1 reverse transcriptase (HIV-RT) are reported that feature extension into the entrance channel near Glu138. Complexes of the parent anilinylpyrimidine 1 and the morpholinoethoxy analog 2j with HIV-RT have received crystallographic characterization confirming the designs. Measurement of aqueous solubilities of 2j, 2k, the parent triazene 2a, and other NNRTIs demonstrate profound benefits for addition of the morpholinyl substituent.
- Bollini, Mariela,Frey, Kathleen M.,Cisneros, José A.,Spasov, Krasimir A.,Das, Kalyan,Bauman, Joseph D.,Arnold, Eddy,Anderson, Karen S.,Jorgensen, William L.
-
p. 5209 - 5212
(2013/09/12)
-
- SUBSTITUTED BENZAMIDES AND THEIR USES
-
Provided herein are Substituted Benzamides, compositions, and method of their manufacture and use.
- -
-
Page/Page column 112-113
(2013/11/05)
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- Synthesis and cellular properties of Near-IR BODIPY-PEG and carbohydrate conjugates
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A series of red and near-IR fluorescent BODIPY conjugates, containing either one or two indolylstyryl groups at the 3- and/or 5-positions and a low molecular weight PEG or carbohydrate group, were synthesized using a Cu(I)-catalyzed azide-alkyne Huisgen cycloaddition ('click' reaction). All BODIPY conjugates show emission and fluorescence quantum yields in the ranges of 642-732 nm and 0.24-0.56, respectively, and Stokes' shifts of ca. 30 nm. In vitro cellular investigations using human carcinoma HEp2 cells showed that all BODIPYs are non-toxic, both in the absence and presence of light (1 J/cm 2), up to 100 μM concentrations. The PEG and galactose conjugates were more efficient at cell internalization than the unconjugated BODIPYs. The mono-indolylstyryl-BODIPYs showed higher cellular uptake (about five-fold) compared with the di-indolylstyryl-BODIPYs, and higher fluorescence quantum yields.
- Uppal, Timsy,Bhupathiraju, N.V.S. Dinesh K.,Vicente, M. Gra?a H.
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supporting information
p. 4687 - 4693
(2013/06/27)
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- Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: Potential applications in bioconjugation and targeted drug delivery
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Herein we describe the sequential synthesis of a variety of azide-alkyne click chemistry-compatible heterobifunctional oligo(ethylene glycol) (OEG) linkers for bioconjugation chemistry applications. Synthesis of these bioorthogonal linkers was accomplished through desymmetrization of OEGs by conversion of one of the hydroxyl groups to either an alkyne or azido functionality. The remaining distal hydroxyl group on the OEGs was activated by either a 4-nitrophenyl carbonate or a mesylate (-OMs) group. The -OMs functional group served as a useful precursor to form a variety of heterobifunctionalized OEG linkers containing different highly reactive end groups, e.g., iodo, -NH2, -SH and maleimido, that were orthogonal to the alkyne or azido functional group. Also, the alkyne- and azide-terminated OEGs are useful for generating larger discrete poly(ethylene glycol) (PEG) linkers (e.g., PEG 16 and PEG24) by employing a Cu(i)-catalyzed 1,3-dipolar cycloaddition click reaction. The utility of these clickable heterobifunctional OEGs in bioconjugation chemistry was demonstrated by attachment of the integrin (αvβ3) receptor targeting peptide, cyclo-(Arg-Gly-Asp-d-Phe-Lys) (cRGfKD) and to the fluorescent probe sulfo-rhodamine B. The synthetic methodology presented herein is suitable for the large scale production of several novel heterobifunctionalized OEGs from readily available and inexpensive starting materials.
- Goswami, Lalit N.,Houston, Zachary H.,Sarma, Saurav J.,Jalisatgi, Satish S.,Hawthorne, M. Frederick
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supporting information
p. 1116 - 1126
(2013/03/28)
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- Using an electrical potential to reversibly switch surfaces between two states for dynamically controlling cell adhesion
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Smart surfaces presenting both antifouling molecules with a charged functional group at their distal end, and molecules that are terminated by RGD peptides for cell adhesion, were fabricated and characterized (see picture). By applying potentials of +300 or -300 mV, the surfaces could be dynamically switched to make the peptide accessible or inaccessible to cells. Copyright
- Ng, Cheuk Chi Albert,Magenau, Astrid,Ngalim, Siti Hawa,Ciampi, Simone,Chockalingham, Muthukumar,Harper, Jason Brian,Gaus, Katharina,Gooding, John Justin
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supporting information; experimental part
p. 7706 - 7710
(2012/08/29)
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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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- Efficient and selective removal of chloroacetyl group promoted with tetra-n-butylammonium fluoride (TBAF)
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A practical method for the efficient and selective cleavage of chloroacetyl protecting group using tetra-n-butylammonium fluoride (TBAF) in THF solution at rt was disclosed.
- Gu, Guofeng,Fang, Min,Du, Yuguo
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experimental part
p. 2801 - 2804
(2012/01/02)
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