- Cofactor-free detection of phosphatidylserine with cyclic peptides mimicking lactadherin
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Cyclic peptides (cLacs) are designed to mimic the natural phosphatidylserine (PS) binding protein lactadherin. Unlike annexin V or its small molecule mimics, the cLac peptides selectively target PS-presenting membranes with no need for metal cofactors. We further show that a fluorophore-labeled cLac effectively stains early apoptotic cells. The small size and facile conjugation with a variety of imaging tracers make the cLac design promising for imaging cell death in vitro as well as in living organisms.
- Zheng, Hong,Wang, Fang,Wang, Qin,Gao, Jianmin
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Read Online
- MERTK 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 00974
(2020/01/31)
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- Self-Assembly and Molecular Recognition in Water: Tubular Stacking and Guest-Templated Discrete Assembly of Water-Soluble, Shape-Persistent Macrocycles
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Supramolecular chemistry in aqueous media is an area with great fundamental and practical significance. To examine the role of multiple noncovalent interactions in controlled assembling and binding behavior in water, the self-association of five water-soluble hexakis(m-phenylene ethynylene) (m-PE) macrocycles, along with the molecular recognition behavior of the resultant assemblies, is investigated with UV-vis, fluorescence, CD, and NMR spectroscopy, mass spectrometry, and computational studies. In contrast to their different extents of self-aggregation in organic solvents, all five macrocycles remain aggregated in water at concentrations down to the micromolar (μM) range. CD spectroscopy reveals that 1-F6 and 1-H6, two macrocycles carrying chiral side chains and capable of H-bonded self-association, assemble into tubular stacks. The tubular stacks serve as supramolecular hosts in water, as exemplified by the interaction of macrocycles 1-H6 and 2-H6 and guests G1 through G4, each having a rod-like oligo(p-phenylene ethynylene) (p-PE) segment flanked by two hydrophilic chains. Fluorescence and 1H NMR spectroscopy revealed the formation of kinetically stable, discrete assemblies upon mixing 2-H6 and a guest. The binding stoichiometry, determined with fluorescence, 1H NMR, and ESI-MS, reveals that the discrete assemblies are novel pseudorotaxanes, each containing a pair of identical guest molecules encased by a tubular stack. The two guest molecules define the number of macrocyclic molecules that comprise the host, which curbs the "infinite" stack growth, resulting in a tubular stack with a cylindrical pore tailoring the length of the p-PE segment of the bound guests. Each complex is stabilized by the action of multiple noncovalent forces including aromatic stacking, side-chain H-bonding, and van der Waals interactions. Thus, the interplay of multiple noncovalent forces aligns the molecules of macrocycles 1 and 2 into tubular stacks with cylindrical inner pores that, upon binding rod-like guests, lead to tight, discrete, and well-ordered tubular assemblies that are unprecedented in water.
- Wang, Qiuhua,Zhong, Yulong,Miller, Daniel P.,Lu, Xiaoxing,Tang, Quan,Lu, Zhong-Lin,Zurek, Eva,Liu, Rui,Gong, Bing
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p. 2915 - 2924
(2020/02/04)
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- NIRF turn-on nanoparticles based on the tumor microenvironment for monitoring intracellular protein delivery
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A dual responsive NIRF turn-on protein delivery system incorporating an NIRF turn-on probe and protein into one single nanoparticle has been constructed. It can be taken up efficiently by A549 cells, where protein release and NIRF recovery happen simultaneously in response to low pH and excessive H2O2. This work provides a novel system for monitoring intracellular protein delivery.
- Xu, Huaibao,Wang, Yi,Pei, Zhichao,Ji, Wei,Pei, Yuxin
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supporting information
p. 14930 - 14933
(2019/12/24)
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- The effect of monosaccharides on self-assembly of benzenetricarboxamides
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The interaction between monosaccharides exhibits an important role in the assembly of monosaccharide-containing molecules. In this work, three common monosaccharides, glucose, galactose and mannose, are employed to investigate the effect of monosaccharide on the self-assembly of benzenetricarboxamide (BTA) core-containing molecules. In the presence of monosaccharides, three benzenetricarboxamide derivatives aggregate into different ordered structures. When alanine linkers are introduced to these molecules between the core and the monosacchride, morphologies of three types of monosaccharide BTAs turned to disordered, meanwhile their structures become similar with the increase of the length of alanine linkers, indicating the disappearance of the monosaccharide effects.
- Wang, Jue,Qi, Wenjing,Chen, Guosong
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p. 587 - 591
(2019/01/04)
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- Multiple arms polymerization target anticancer conjugate
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Disclosed is a multi-arm targeting drug conjugate modified by a water-soluble polymer; the drug conjugate has the structural formula of (III). In formula (III), R is an organic core, POLY is a polymer, L is a multivalent linker, T is a targeting molecule, D is a camptothecin-based drug, and q is any integer between 3 and 8. The drug conjugate may improve the poor water solubility, high toxicity and low bioavailability of camptothecin-based drugs.
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- Targeting multi-arm conjugate (by machine translation)
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The present invention discloses a multi-arm, by the water-soluble polymer modified folic acid receptor targeted drug conjugates and salts thereof. The drug conjugate has the following structural formula: The invention is a multi-arm polymer modified targeting anticancer conjugate, wherein the water-soluble polymer may be modified to enhance the water solubility of the conjugate, thereby increasing the drug loading. In the invention of targeting molecules for folic acid, folic acid as a targeting molecule, folic acid receptor expressing abundant active targeting of tumor cells, play a better anti-tumor efficacy, increase target, and thus make the concentration of the conjugate in the targeted tissue more high. (by machine translation)
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- SMALL MOLECULE INHIBITORS OF CANCER STEM CELLS AND MESENCHYMAL CANCER TYPES
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The present disclosure provides compounds, their pharmaceutical compositions, and methods of their use for treating mesenchymally-derived or mesenchymallytransformed cancers, such as breast cancers and sarcomas, and for treating diseases or disorders that are characterized by the expression of vimentin.
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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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- Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy
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Photodynamic therapy (PDT) is a promising treatment strategy for malignant and nonmalignant lesions. 5-Aminolaevulinic acid (ALA) is used as a precursor of the photosensitizer, protoporphyrin IX (PpIX), in dermatology and urology. However, the effectiveness of ALA-PDT is limited by the relatively poor bioavailability of ALA and rapid conversion of PpIX to haem. The main goal of this study was to prepare and investigate a library of single conjugates designed to coadminister the bioactive agents ALA and hydroxypyridinone (HPO) iron chelators. A significant increase in intracellular PpIX levels was observed in all cell lines tested when compared to the administration of ALA alone. The higher PpIX levels observed using the conjugates correlated well with the observed phototoxicity following exposure of cells to light. Passive diffusion appears to be the main mechanism for the majority of ALA-HPOs investigated. This study demonstrates that ALA-HPOs significantly enhance phototherapeutic metabolite formation and phototoxicity.
- Battah, Sinan,Hider, Robert C.,MacRobert, Alexander J.,Dobbin, Paul S.,Zhou, Tao
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p. 3498 - 3510
(2017/05/05)
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- Azo-based connection unit of the fluorescence-labeled nucleotide and its use
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The invention provides an azo linkage unit based fluorescence labeled nucleotide and applications thereof. The structural formula of the nucleotide is shown in a formula VI in the specification, wherein fluorescein is selected from one of BODIPY, rhodamine, coumarin, xanthene, cyanin, pyrene, phthalocyanine, Alexa, Squaring dye, a combination producing energy transfer dyes and derivatives thereof; R1, R2, R3 R4 and R6 are various substituent groups, R5 is a substituent group except -C2H5, and R1, R2, R3, R4, R5 and R6 are not H simultaneously; and n is an integer between 0 and 10. Compared with the prior art, a kind of new azo linkage unit based reversible terminals is synthesized according to the invention; the kind of reversible terminals can realize high-efficiency shearing under moderate conditions, so that the kind of reversible terminals can be used for DNA sequencing; and raw materials required by synthesis are simple and easy to obtain, and reactions in the synthetic process are all conventional chemical reactions, therefore, the nucleotide can be subjected to large-scale promotion and application.
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Paragraph 0073; 0075
(2018/01/11)
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- ALKYNYL INDAZOLE DERIVATIVE AND USE THEREOF
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The main object of the present invention is to provide a novel compound which has a VEGF receptor tyrosine kinase inhibitory activity and is useful as an active ingredient for the treatment of diseases accompanying angiogenesis or edema, for example, age-related macular degeneration or the like. The present invention includes, for example, an alkynyl indazole derivative represented by the following general formula (I), a pharmaceutical acceptable salt thereof, and a medicine containing thereof.
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Paragraph 0261; 0262
(2017/02/24)
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- Thermoresponsive dendronized copolymers for protein recognitions based on biotin–avidin interaction
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Thermoresponsive biotinylated dendronized copolymers carrying dendritic oligoethylene glycol (OEG) pendants were prepared via free radical polymerization, and their protein recognitions based on biotin–avidin interaction investigated. Both first (PG1) and second generation (PG2) dendronized copolymers were designed to examine possible thickness effects on the interaction between biotin and avidin. Inherited from the outstanding thermoresponsive properties from OEG dendrons, these biotinylated cylindrical copolymers show characteristic thermoresponsive behavior which provides an envelope to capture avidin through switching temperatures above or below their phase transition temperatures (Tcps). Thus, the recognition of polymer-supported biotin with avidin was investigated with UV/vis spectroscopy and dynamic laser light scattering. In contrast to the case for PG1, the increased thickness for copolymer PG2 hinders partially and inhibits the recognition of biotin moieties with avidin either below or above its Tcp. This demonstrates the significant architecture effects from dendronized polymers on the biotin moieties to shift onto periphery of the collapsed aggregates, which should be a prerequisite for protein recognition. These kinds of novel thermoresponsive copolymers may pave a way for the interesting biological applications in areas such as reversible activity control of enzyme or proteins, and for controlled delivery of drugs or genes.
- Zhou, Chunhua,Abdel-Rahman, Mona A.,Li, Wen,Liu, Kun,Zhang, Afang
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p. 832 - 838
(2017/05/16)
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- Hydrophilic and Cell-Penetrable Pyrrolidinyl Peptide Nucleic Acid via Post-synthetic Modification with Hydrophilic Side Chains
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Peptide nucleic acid (PNA) is a nucleic acid mimic in which the deoxyribose-phosphate was replaced by a peptide-like backbone. The absence of negative charge in the PNA backbone leads to several unique behaviors including a stronger binding and salt independency of the PNA-DNA duplex stability. However, PNA possesses poor aqueous solubility and cannot directly penetrate cell membranes. These are major obstacles that limit in vivo applications of PNA. In previous strategies, the PNA can be conjugated to macromolecular carriers or modified with positively charged side chains such as guanidinium groups to improve the aqueous solubility and cell permeability. In general, a preformed modified PNA monomer was required. In this study, a new approach for post-synthetic modification of PNA backbone with one or more hydrophilic groups was proposed. The PNA used in this study was the conformationally constrained pyrrolidinyl PNA with prolyl-2-aminocyclopentanecarboxylic acid dipeptide backbone (acpcPNA) that shows several advantages over the conventional PNA. The aldehyde modifiers carrying different linkers (alkylene and oligo(ethylene glycol)) and end groups (-OH, -NH2, and guanidinium) were synthesized and attached to the backbone of modified acpcPNA by reductive alkylation. The hybrids between the modified acpcPNAs and DNA exhibited comparable or superior thermal stability with base-pairing specificity similar to those of unmodified acpcPNA. Moreover, the modified apcPNAs also showed the improvement of aqueous solubility (10-20 folds compared to unmodified PNA) and readily penetrate cell membranes without requiring any special delivery agents. This study not only demonstrates the practicality of the proposed post-synthetic modification approach for PNA modification, which could be readily applied to other systems, but also opens up opportunities for using pyrrolidinyl PNA in various applications such as intracellular RNA sensing, specific gene detection, and antisense and antigene therapy.
- Pansuwan, Haruthai,Ditmangklo, Boonsong,Vilaivan, Chotima,Jiangchareon, Banphot,Pan-In, Porntip,Wanichwecharungruang, Supason,Palaga, Tanapat,Nuanyai, Thanesuan,Suparpprom, Chaturong,Vilaivan, Tirayut
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p. 2284 - 2292
(2017/09/26)
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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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- Spacer structure and hydrophobicity influences transfection activity of novel polycationic gemini amphiphiles
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Three novel polycationic gemini amphiphiles with different spacers were developed and evaluated in terms of their physiochemical properties and transfection efficiencies. Cationic liposomes formed by these amphiphiles and the helper lipid DOPE were able to successfully condense DNA, as shown by gel mobility shift and ethidium bromide intercalation assays. Transfection activity of the liposomes was superior to Lipofectamine 2000 and was dependent on spacer structure, hydrophobicity, and nucleic acid type (pDNA or siRNA). We demonstrated that the cationic liposomes 2X6/DOPE and 2X7/DOPE are potential non-toxic vehicles for gene delivery.
- Puchkov, Pavel A.,Kartashova, Irina A.,Shmendel, Elena V.,Luneva, Anastasya S.,Morozova, Nina G.,Zenkova, Marina A.,Maslov, Mikhail A.
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p. 3284 - 3288
(2017/07/07)
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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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- Tandem photoaffinity labeling of a target protein using a linker with biotin, alkyne and benzophenone groups and a bioactive small molecule with an azide group
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A novel linker containing biotin, alkyne and benzophenone groups (1) was synthesized to identify target proteins using a small molecule probe. This small molecule probe contains an azide group (azide probe) that reacts with an alkyne in 1 via an azide- alkyne Huisgen cycloaddition. Cross-linking of benzophenone to the target protein formed a covalently bound complex consisting of the azide probe and the target protein via 1. The biotin was utilized via biotin-avidin binding to identify the cross-linked complex. To evaluate the effectiveness of 1, it was applied in a model system using an allene oxide synthase (AOS) from the model moss Physcomitrella patens (PpAOS1) and an AOS inhibitor that contained azide group (3). The cross-linked complex consisting of PpAOS1, 1 and 3 was resolved via SDS-PAGE and visualized using a chemiluminescent system. The method that was developed in this study enables the effective identification of target proteins.
- Anabuki, Tomoaki,Tsukahara, Miu,Matsuura, Hideyuki,Takahashi, Kosaku
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p. 432 - 439
(2016/03/01)
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- Covalent Protein Labeling by Enzymatic Phosphocholination
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We present a new protein labeling method based on the covalent enzymatic phosphocholination of a specific octapeptide amino acid sequence in intact proteins. The bacterial enzyme AnkX from Legionella pneumophila has been established to transfer functional phosphocholine moieties from synthetically produced CDP-choline derivatives to N-termini, C-termini, and internal loop regions in proteins of interest. Furthermore, the covalent modification can be hydrolytically removed by the action of the Legionella enzyme Lem3. Only a short peptide sequence (eight amino acids) is required for efficient protein labeling and a small linker group (PEG-phosphocholine) is introduced to attach the conjugated cargo.
- Heller, Katharina,Ochtrop, Philipp,Albers, Michael F.,Zauner, Florian B.,Itzen, Aymelt,Hedberg, Christian
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p. 10327 - 10330
(2015/09/01)
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- Toward multifunctional "clickable" diamond nanoparticles
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Nanodiamonds (NDs) are among the most promising new carbon based materials for biomedical applications, and the simultaneous integration of various functions onto NDs is an urgent necessity. A multifunctional nanodiamond based formulation is proposed here. Our strategy relies on orthogonal surface modification using different dopamine anchors. NDs simultaneously functionalized with triethylene glycol (EG) and azide (N3) functions were fabricated through a stoichiometrically controlled integration of the dopamine ligands onto the surface of hydroxylated NDs. The presence of EG functionalities rendered NDs soluble in water and biological media, while the N3 group allowed postsynthetic modification of the NDs using "click" chemistry. As a proof of principle, alkynyl terminated di(amido amine) ligands were linked to these ND particles.
- Khanal, Manakamana,Turcheniuk, Volodymyr,Barras, Alexandre,Rosay, Elodie,Bande, Omprakash,Siriwardena, Aloysius,Zaitsev, Vladimir,Pan, Guo-Hui,Boukherroub, Rabah,Szunerits, Sabine
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p. 3926 - 3933
(2015/04/14)
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- Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin
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The molecular recognition of carbohydrates and proteins mediates a wide range of physiological processes and the development of synthetic carbohydrate receptors ("synthetic lectins") constitutes a key advance in biomedical technology. In this article we report a synthetic lectin that selectively binds to carbohydrates immobilized in a molecular monolayer. Inspired by our previous work, we prepared a fluorescently labeled synthetic lectin consisting of a cyclic dimer of the tripeptide Cys-His-Cys, which forms spontaneously by air oxidation of the monomer. Amine-tethered derivatives of N-acetylneuraminic acid (NANA), β-D-galactose, β-Dglucose and α-D-mannose were microcontact printed on epoxide-terminated self-assembled monolayers. Successive prints resulted in simple microarrays of two carbohydrates. The selectivity of the synthetic lectin was investigated by incubation on the immobilized carbohydrates. Selective binding of the synthetic lectin to immobilized NANA and β-D-galactose was observed by fluorescence microscopy. The selectivity and affinity of the synthetic lectin was screened in competition experiments. In addition, the carbohydrate binding of the synthetic lectin was compared with the carbohydrate binding of the lectins concanavalin A and peanut agglutinin. It was found that the printed carbohydrates retain their characteristic selectivity towards the synthetic and natural lectins and that the recognition of synthetic and natural lectins is strictly orthogonal.
- Rauschenberg, Melanie,Fritz, Eva-Corrina,Schulz, Christian,Kaufmann, Tobias,Ravoo, Bart Jan
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p. 1354 - 1364
(2014/07/22)
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- Fabrication of highly stable glyco-gold nanoparticles and development of a glyco-gold nanoparticle-based oriented immobilized antibody microarray for lectin (GOAL) assay
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The design of high-affinity lectin ligands is critical for enhancing the inherently weak binding affinities of monomeric carbohydrates to their binding proteins. Glyco-gold nanoparticles (glyco-AuNPs) are promising multivalent glycan displays that can confer significantly improved functional affinity of glyco-AuNPs to proteins. Here, AuNPs are functionalized with several different carbohydrates to profile lectin affinities. We demonstrate that AuNPs functionalized with mixed thiolated ligands comprising glycan (70 mol%) and an amphiphilic linker (30 mol%) provide long-term stability in solutions containing high concentrations of salts and proteins, with no evidence of nonspecific protein adsorption. These highly stable glyco-AuNPs enable the detection of model plant lectins such as Concanavalin A, wheat germ agglutinin, and Ricinus communis Agglutinin 120, at subnanomolar and low picomolar levels through UV/Vis spectrophotometry and dynamic light scattering, respectively. Moreover, we develop in situ glyco-AuNPs-based agglutination on an oriented immobilized antibody microarray, which permits highly sensitive lectin sensing with the naked eye. In addition, this microarray is capable of detecting lectins presented individually, in other environmental settings, or in a mixture of samples. These results indicate that glyconanoparticles represent a versatile and highly sensitive method for detecting and probing the binding of glycan to proteins, with significant implications for the construction of a variety of platforms for the development of glyconanoparticle-based biosensors.
- Huang, Li-De,Adak, Avijit K.,Yu, Ching-Ching,Hsiao, Wei-Chen,Lin, Hong-Jyune,Chen, Mu-Lin,Lin, Chun-Cheng
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supporting information
p. 3956 - 3967
(2015/10/19)
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- Photoactivable nonsymmetrical bifunctional linkers for protein immobilization on attenuated total reflectance FTIR optical devices
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The photosensitive 4-azido-2,3,5,6-tetrafluoro-1-benzoyl core has been connected to maleimide-, chloroacetyloxy-, or succinimidyl carbonate motifs through various spacers to furnish a series of bifunctional linkers. One linker (7a) has been used for the construction of a biosensor for β-lactam antibiotic detection by attenuated total reflectance FTIR (ATR-FTIR) spectroscopy. Linkers featuring a photosensitive aryl azide motif at one end and a function reactive toward nucleophiles at the other end are described. One linker is used for the construction of a biosensor for β-lactam antibiotic detection by attenuated total reflectance FTIR spectroscopy. Copyright
- Hammaecher, Catherine,Joris, Bernard,Goormaghtigh, Erik,Marchand-Brynaert, Jacqueline
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p. 7952 - 7959
(2014/01/06)
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- High-affinity fluorescent ligands for the 5-HT3 receptor
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The synthesis, photophysical and biological characterization of a small library of fluorescent 5-HT3 receptor ligands is described. Several of these novel granisetron conjugates have high quantum yields and show high affinity for the human 5-HT3AR.
- Simonin, Jonathan,Vernekar, Sanjeev Kumar V.,Thompson, Andrew J.,Hothersall, J. Daniel,Connolly, Christopher N.,Lummis, Sarah C.R.,Lochner, Martin
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p. 1151 - 1155
(2012/03/26)
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- LDV peptidomimetics equipped with biotinylated spacer-arms: Synthesis and biological evaluation on CCRF-CEM cell line
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The tripeptide Leu-Asp-Val (LDV) is known to bind α4β 1 integrin in leukemia cells. Here we have synthesized a LDV peptidomimetic equipped with a biotin-conjugated spacer-arm. Compound 9 acts as an inhibitor of the α4β1 integrin in an adhesion assay using fluorescently labeled, α4β 1 integrin-expressing leukemia CCRF-CEM cells. Furthermore, when bound to neutravidin-coated plates, compound 9 could capture CCRF-CEM cells. Such biotin-conjugated LDV peptidomimetic may thus represent a novel tool for biotechnological applications using avidin interaction for leukapheresis or leukemia cell targeting.
- Gérard, Estelle,Meulle, Aline,Feron, Olivier,Marchand-Brynaert, Jacqueline
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supporting information; experimental part
p. 586 - 590
(2012/03/26)
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- Self-calibrating viscosity probes: Design and subcellular localization
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We describe the design, synthesis and fluorescence profiles of new self-calibrating viscosity dyes in which a coumarin (reference fluorophore) has been covalently linked with a molecular rotor (viscosity sensor). Characterization of their fluorescence properties was made with separate excitation of the units and through resonance energy transfer from the reference to the sensor dye. We have modified the linker and the substitution of the rotor in order to change the hydrophilicity of these probes thereby altering their subcellular localization. For instance, hydrophilic dye 12 shows a homogeneous distribution inside the cell and represents a suitable probe for viscosity measurements in the cytoplasm.
- Dakanali, Marianna,Do, Thai H.,Horn, Austin,Chongchivivat, Akaraphon,Jarusreni, Tuptim,Lichlyter, Darcy,Guizzunti, Gianni,Haidekker, Mark A.,Theodorakis, Emmanuel A.
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experimental part
p. 4443 - 4450
(2012/08/28)
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- A convenient route to diversely substituted icosahedral closomer nanoscaffolds
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The design and synthesis of icosahedral polyhedral borane closomer motifs based upon carbonate and carbamate anchoring groups for biomedical applications are described. Dodecacarbamate closomers containing easily accessible groups of interest at their linker termini were synthesized via activation of the B-OH vertices as aryl carbonates and their subsequent reaction with primary amines. Novel dodecacarbonate closomers were successfully synthesized for the first time by reacting [closo-B12(OH)12]2- with an excess of respective aryl chloroformates, utilizing relatively short reaction times, mild conditions and simple purification strategies, all of which had previously presented difficulties in closomer chemistry. This methodology for the 12-fold degenerate synthesis of carbonate and carbamate closomers will greatly facilitate further exploration of closomers as monodisperse nanomolecular delivery platforms.
- Jalisatgi, Satish S.,Kulkarni, Vikas S.,Tang, Betty,Houston, Zachary H.,Lee, Mark W.,Hawthorne, M. Frederick
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supporting information; scheme or table
p. 12382 - 12385
(2011/10/02)
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- Synthesis of N-propynyl analogues of peptide nucleic acid (PNA) monomers and their use in the click reaction to prepare N-functionalized PNAs
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Application of the click reaction for coupling a 2-(2-aminoethoxy)ethoxy (AEE) function to thyminyl, cytosinyl and adeninyl peptide nucleic acid (PNA) monomer analogues bearing a N-propynyl group, in place of the original N-2-aminoethyl moiety, has been explored. The N-propynyl PNA analogues were prepared from glycine ethyl ester hydrochloride and the structure of the thyminyl derivative was confirmed by X-ray diffraction. These monomers were employed in click reactions with Boc-protected AEE azide to afford the corresponding triazolyl-linked PNA-AEE conjugates in yields ranging from 64 to 76%. [1,4]-Regiochemistry was verified from a NOESY correlation experiment.
- Howarth, Nicola M.,Ricci, Jennyfer
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experimental part
p. 9588 - 9594
(2011/12/14)
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- Zinc(II)cyclen-peptide conjugates interacting with the weak effector binding state of Ras
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Zinc(II)cyclen-peptide hybrid compounds and bis-zinc(II)cyclen complexes are prepared as potential binders of the guanine nucleotide binding protein Ras, an important molecular switch in cellular signal transduction. The design of the compounds is based on the previous observation that zinc(II)cyclen complexes could serve as lead compounds for inhibitors of Ras-effector interaction and thus be able to interrupt Ras induced signal transduction. Zinc(II)cyclen selectively stabilizes conformational state 1 of active Ras, a conformational state with drastically decreased affinity to effector proteins like Raf-kinase. To achieve higher binding affinities of such Ras-Raf interaction inhibitors, zinc(II)cyclen conjugates with short peptides, derived from the sequence of the Ras-activator SOS, were prepared by solid phase synthesis protocols. Dinuclear bis-zinc(II)cyclen complexes were obtained from alkyne-azide cycloaddition reactions. NMR investigations of the prepared compounds revealed that the peptide conjugates do not lead to an increase in Ras binding affinity of the metal complex-peptide conjugates. The dinuclear zinc complexes lead to an immediate precipitation of the protein prohibiting spectroscopic investigations of their binding.
- Schmidt, Florian,Rosnizeck, Ina C.,Spoerner, Michael,Kalbitzer, Hans Robert,K?nig, Burkhard
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- Modular synthesis of bifunctional linkers for materials science
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A practical synthesis of α,ω-bifunctional linkers is described that is based on three building blocks, namely, thioctic acid, a spacer-arm of seven ethylene glycol units, and a functional motif dedicated to the selective immobilization of purposely tagged proteins. Such representative motifs are biotin, haloacetamide, maleimide, and nitrilotriacetic acid derivatives. The building blocks are connected through alkyl, amide, and/or carbamate linkages. Copyright
- Moreau, Julie,Marchand-Brynaert, Jacqueline
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p. 1641 - 1644
(2011/05/03)
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- One-pot synthesis of polyrotaxane by clipping and cyclopolymerization of α,ω-diethynyl isophthalamide with pyridiniumdicarboxamide chloride
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The one-pot synthesis of a main chain-type polyrotaxane composed of axle molecules threaded through the macrocyclic units on the polymer main chain was achieved via the combination of cyclopolymerization and clipping procedures. The cyclopolymerization of an α,ω-diethynyl monomer bearing an isophthalamide moiety (1), which clips onto an axle component bearing a pyridiniumdicarboxamide moiety (2Cl) through a chloride anion was carried out in chloroform with the monomer concentration of 0.06 mol L-1 at 40 °C using [Rh(nbd)Cl]2/Et3N as a catalyst to afford a gel-free polymer. The resulting polymer was assigned to the main chain-type polyrotaxane with a poly(phenylacetylene) backbone (poly-3Cl) based on size exclusion chromatography and 1H NMR measurements. The diffusion-order two-dimensional NMR and circular dichroism spectra provided definitive proof of the rotaxaned architecture in the polymer. The mole fraction of the rotaxane unit in the total cyclic repeating unit was determined to be 26.3%.
- Isono, Takuya,Satoh, Toshifumi,Kakuchi, Toyoji
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experimental part
p. 3184 - 3192
(2012/05/05)
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- Novel 3-O-pegylated carboxylate and 3-O-pegylated carbamate prodrugs of naltrexone for microneedle-enhanced transdermal delivery
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A small library of novel 3-O-pegylated carboxylate prodrugs (4a-4b) and 3-O-pegylated carbamate prodrugs (9a-9b) of naltrexone were synthesized. The goal behind the design of these prodrugs was to investigate their potential for microneedle-enhanced transdermal delivery. All the synthesized 3-O-pegylated carboxylate prodrugs (4a-4b) and 3-O-pegylated carbamate prodrugs (9a-9b) of naltrexone were found to have adequate stability in a transdermal formulation and improved apparent solubility compared to naltrexone. Viscosity effects were postulated to be responsible for the observed non-linearity in the flux-concentration profile of these prodrugs.
- Yerramreddy, Thirupathi Reddy,Milewski, Mikolaj,Penthala, Narsimha Reddy,Stinchcomb, Audra L.,Crooks, Peter A.
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scheme or table
p. 3280 - 3283
(2010/08/19)
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- Porphyrin based molecular turnstiles
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Molecular turnstiles, based on a hinge composed of a Sn-porphyrin bearing coordinating sites at the meso positions and a handle, equipped with a tridentate coordinating pole or its Pd(ii) complex, connected to the porphyrin through Sn-O bonds, offering open (free rotation of the handle around the hinge) and close states (blockage of rotation through binding of Pd(ii)) were designed, prepared and studied both in solution and in the solid state.
- Lang, Thomas,Guenet, Aurelie,Graf, Ernest,Kyritsakas, Nathalie,Hosseini, Mir Wais
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supporting information; experimental part
p. 3508 - 3510
(2010/08/06)
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- Potent ligands for prokaryotic UDP-galactopyranose mutase that exploit an enzyme subsite
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UDP-Galactopyranose mutase (UGM or Glf), which catalyzes the interconversion of UDP-galactopyranose and UDP-galactofuranose, is implicated in the viability and virulence of multiple pathogenic microorganisms. Here we report the synthesis of high-affinity ligands for UGM homologues from Klebsiella pneumoniae and Mycobacterium tuberculosis. The potency of these compounds stems from their ability to access both the substrate binding pocket and an adjacent site.
- Dykhuizen, Emily C.,Kiessling, Laura L.
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supporting information; experimental part
p. 193 - 196
(2009/06/28)
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- INHIBITORS OF UDP-GALACTOPYRANOSE MUTASE THWART MYCOBACTERIAL GROWTH
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Compounds which inhibit microbial growth or attenuate the virulence of pathogen microorganisms. Compounds of the invention inhibit UDP-galactopyranose mutase (UGM) and have activity as inhibitors of microbial growth of microorganisms which contain this enzyme and particularly those microorganisms in which this enzyme is responsible for the incorporation of galactofuranose residues, particularly for uridine 5'-diphosphate (UDP) galactopyranose mutase. Compounds of the invention inhibit UDP- galactopyranose mutase (UGM) and have activity to attenuate virulence of pathogenic microorganisms, including mycobacteria.
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Page/Page column 65-66
(2009/12/05)
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- PHOSPHORAMIDITE NUCLEOSIDE ANALOGS
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Described are phosphoramidite nucleoside analog monomers, precursors thereof, and oligonucleotides including one or more of the monomers. The monomers can be used during automated synthesis of oligonucleotide derivatives, and allow for incorporation of one or several reporter groups, organic molecules, bio-molecules, small molecules or other chemical groups at the internucleoside phosphotriesters. Oligonucleotides including the monomers have a number of uses in therapeutic, diagnostic, and research applications.
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Page/Page column 25-26
(2009/04/25)
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- A graftable LDV peptidomimetic: Design, synthesis and application to a blood filtration membrane
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A graftable LDV (Leu-Asp-Val) peptidomimetic molecule (B-c) has been prepared from 3-(5-amino-2-hydroxy)phenyl-propionic acid, as α4β1 (VLA-4) integrin ligand. For that purpose, the mechanism of 3-(4-azidophenyl)propionic acid rearrangement has been revisited. Activation of Durapore DVPP-hydrophilic membrane, by surface wet chemistry using triazine trifluoride, followed by covalent coupling of B-c produced a modified filter (0.8% of derivatisation from XPS analysis) with improved capacity of leukocyte retention.
- Momtaz, Maryam,Rerat, Vincent,Gharbi, Sonia,Gerard, Estelle,Pourcelle, Vincent,Marchand-Brynaert, Jacqueline
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p. 1084 - 1090
(2008/09/18)
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- A novel thymidine phosphoramidite synthon for incorporation of internucleoside phosphate linkers during automated oligodeoxynucleotide synthesis
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A novel thymidine phosphoramidite synthon was synthesized and successfully used for incorporation of primary amino groups, attached through a triethylene glycol linker to the internucleoside phosphates, at desired locations during automated oligodeoxynucleotide synthesis. The synthesized amino-linker bearing oligonucleotides are stable under deprotection conditions and exhibit Watson-Crick base-pairing properties. Covalent labeling of oligonucleotides with carbocyanine near-infrared fluorochromes resulted in 2.5 times higher labeling yields when compared with oligonucleotides containing base-attached aminolinkers. We anticipate that the developed synthetic approach will be useful for nucleotide sequence-specific attachment of single or multiple ligands or reporter molecules. Copyright Taylor & Francis Group, LLC.
- Tabatadze, David,Zamecnik, Paul,Yanachkov, Ivan,Wright, George,Pierson, Katherine,Zhang, Surong,Bogdanov Jr., Alexei,Metelev, Valeri
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p. 157 - 172
(2008/09/18)
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- Synthesis and evaluation of a small library of graftable thrombin inhibitors derived from (l)-arginine
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Novel piperazinyl-amide derivatives of N-α-(aryl-sulfonyl)-l-arginine were synthesized as graftable thrombin inhibitors, in the context of biomaterials' design. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position and the introduction of a trifluoromethyl group as XPS (X-ray Photoelectron Spectroscopy) tag on the sulfonamide moiety were evaluated in vitro against human α-thrombin. All the compounds of the library were found to be active at the micromolar level, as the reference TAME (N-tosyl-l-arginine methyl ester). The blood compatibilization improvement of poly(ethylene terephthalate) (PET) membrane, coated or grafted by wet chemistry treatment with one representative inhibitor of the library, was also evaluated, showing interesting decrease in blood clot formation.
- Salvagnini, Claudio,Gharbi, Sonia,Boxus, Thierry,Marchand-Brynaert, Jacqueline
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- Design and synthesis of a novel photoaffinity taxoid as a potential probe for the study of paclitaxel-microtubules interactions
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A novel and non-radioactive bifunctional photoaffinity probe (BPP) for the study of paclitaxel-microtubules interactions is designed and synthesized. This new BPP-taxoid bears a 3-nitro-5-trifluoromethyl- diazirinyl-phenoxyacetyl group at C-3'N for photoaffinity/photocleavage and a biotin subunit at C-7 for affinity chromatography. (C) 2000 Elsevier Science Ltd.
- Lin, Songnian,Fang, Kan,Hashimoto, Masaru,Nakanishi, Koji,Ojima, Iwao
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p. 4287 - 4290
(2007/10/03)
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- Cleavable bifunctional coupling agents
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A bifunctional coupling agent for joining a sulfhydryl containing protein or peptide and a metallic radionuclide comprising a sulfhydryl selective electrophile, a chelator containing at least one protected thiol and a organic linking radical containing at least one cleavable site which serves to join said electrophile and said chelator is disclosed. A radiodiagnostic or radiotherapeutic precursor comprising an antibody or antibody fragment and the specified bifunctional coupling agent bound to a sulfhydryl group on the antibody or antibody fragment and a radiodiagnostic or radiotherapeutic agent comprising such precursor having a metallic radionuclide bound thereto are also disclosed.
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- Synthesis of New Phospholipids Linked to Steroid-Hormone Derivatives Designed for Two-Dimensional Crystallization of Proteins
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The synthesis of phospholipids 1n-3n, rationally designed for two-dimensional crystallization of progesterone and estradiol receptors, is reported.The structure of theses lipids provides them with essential properties such as fluidity and stability when spread into monolayers at the air/H2O interface, affinity for the protein to be crystallized, and accessibility of the ligand under the lipid monolayer.
- Lebeau, Luc,Oudet, Pierre,Mioskowski, Charles
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p. 1697 - 1706
(2007/10/02)
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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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- INTRAMOLECULAR CYCLIZATION OF N,N-Di(OLIGOOXYETHYLENE)AMINES: A NEW SYNTHESIS OF MONOAZA CROWN ETHERS
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The reaction of N,N-di(oligooxyethylene)amines with arenesulfonyl chloride in the presence of alkali metal hydroxide was investigated.It was found that the monoarenesulfonates of N,N-di(oligooxyethylene)amines were first formed as intermediates, and their subsequent intramolecular cyclization gave N-unsubstituted monoaza crown ethers rather selectively.
- Maeda, Hirokazu,Furuyoshi, Shigeo,Nakatsuji, Yohji,Okahara, Mitsuo
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p. 3359 - 3362
(2007/10/02)
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