88192-19-2Relevant articles and documents
Fit to be tied: Conformation-directed macrocyclization of peptoid foldamers
Holub, Justin M.,Jang, Hangjun,Kirshenbaum, Kent
, p. 3275 - 3278 (2007)
Covalent macrocyclic constraints can be readily installed on N-substituted glycine "peptoid" oligomer substrates. Cu(I)-catalyzed [3+2] cycloaddition reactions were conducted on solid support to ligate peptoid side chain azide and alkyne functionalities. Intramolecular macrocycle formation is facilitated by preorganizing the reactive groups across one turn of the helical secondary structure. These results confirm that conformational ordering can be exploited to assist the macrocyclization of folded oligomers.
Multivalent peptidomimetic conjugates: A versatile platform for modulating androgen receptor activity
Levine, Paul M.,Imberg, Keren,Garabedian, Michael J.,Kirshenbaum, Kent
, p. 6912 - 6915 (2012)
We introduce a family of multivalent peptidomimetic conjugates that modulate the activity of the androgen receptor (AR). Bioactive ethisterone ligands were conjugated to a set of sequence-specific peptoid oligomers. Certain multivalent peptoid conjugates enhance AR-mediated transcriptional activation. We identify a linear and a cyclic conjugate that exhibit potent anti-proliferative activity in LNCaP-abl cells, a model of therapy-resistant prostate cancer. The linear conjugate blocks AR action by competing for ligand binding. In contrast, the cyclic conjugate is active despite its inability to compete against endogenous ligand for binding to AR in vitro, suggesting a non-competitive mode of action. These results establish a versatile platform to design competitive and non-competitive AR modulators with potential therapeutic significance.
Synthesis and single enzyme activity of a clicked lipase-BSA hetero-dimer
Hatzakis, Nikos S.,Engelkamp, Hans,Velonia, Kelly,Hofkens, Johan,Christianen, Peter C. M.,Svendsen, Allan,Patkar, Shamkantr A.,Vind, Jesper,Maan, Jan C.,Rowan, Alan E.,Nolte, Roeland J. M.
, p. 2012 - 2014 (2006)
Click chemistry is used to construct a novel lipase-BSA hetero-dimer, in which the latter protein acts as a foot enabling the anchoring of the enzyme onto the surface for single enzyme studies. The Royal Society of Chemistry 2006.
Hypoxia-Activated and Indomethacin-Mediated Theranostic Prodrug Releasing Drug On-Demand for Tumor Imaging and Therapy
Peng, Xiaoran,Gao, Jiaxin,Yuan, Yumeng,Liu, Haitong,Lei, Weiyan,Li, Shenghui,Zhang, Jinchao,Wang, Shuxiang
, p. 2828 - 2843 (2019)
A smart theranostic prodrug IMC-FDU-TZBC-NO2, releasing active drug on-demand based on hypoxia-activated and indomethacin-mediated, for solid tumor imaging and efficient therapy was designed. This prodrug was constructed by conjugating chemotherapy drug 5-fluoro-2-deoxyuridine (FDU), targeting moiety indomethacin (IMC), and the hypoxic trigger 4-nitrobenzyl group to a fluorescent dye precursor, which was mediated by IMC and activated by NTR under hypoxic conditions. The fluorescent dye IMC-TZBCM was generated and FDU was released at the same time in tumor cells. The rates and amounts of FDU release and IMC-TZBCM generation were regulated by hypoxia status, and increased with increasing degree of hypoxia. Nevertheless, it is "locked" in normal cells. It combined the advantages of tumor targeting, diagnosis, and chemotherapy functions, showed excellent targeting ability to cancer cells, excellent stability in physiological conditions, high cellular uptake efficiency, and on-demand drug release behavior. The in vitro and in vivo assays demonstrated that IMC-FDU-TZBC-NO2 exhibits enhanced anticancer potency and low side effects. The novel targeted theranostic prodrug activated by hypoxia shows a great potential in cancer therapy.
Cyclodextrin-/photoisomerization-modulated assembly and disassembly of an azobenzene-grafted polyoxometalate cluster
Li, Hongbo,Jiang, Fengrui,Zhang, Guohua,Li, Bao,Wu
, p. 5168 - 5175 (2019)
Herein, a mono-lacunary Keggin-type polyoxometalate (POM), [SiW11O39]8?, grafted with an azobenzene group through Sn ion bridging was prepared, and the formed organic-inorganic hybrid cluster was characterized via elemental analysis, NMR, TGA, and IR techniques. A vesicular structure of the hybrid cluster assembly in aqueous media was observed in the TEM image, and it dissociated in the presence of α-/β-, γ-cyclodextrins (α-/β-, γ-CDs); this dissociation was driven by the host-guest interactions. The monodispersed inclusion complex further reassembled into smaller micelles under irradiation with 365 nm light, and this transformation was reversibly controlled by alternating the irradiation with 450 nm light. Moreover, in the case of the POM-Azo/β-CD system, reassembly from the monodispersed state to the vesicular state was achieved by the addition of a competitive guest molecule. Thus, the reversible host-guest interactions combining reversible photoisomerization of the azobenzene group provided multiple ways to modulate the assembly and disassembly of the POM hybrid as well as the changes between different assemblies. The present study inspires the potential use of these kind of hybrid POMs in enhanced catalytic reactions and recycling.
MRI-visible poly(ε-caprolactone) with controlled contrast agent ratios for enhanced visualization in temporary imaging applications
El Habnouni, Sarah,Nottelet, Benjamin,Darcos, Vincent,Porsio, Barbara,Lemaire, Laurent,Franconi, Florence,Garric, Xavier,Coudane, Jean
, p. 3626 - 3634 (2013)
Hydrophobic macromolecular contrast agents (MMCAs) are highly desirable to provide safe and efficient magnetic resonance (MR) visibility to implantable medical devices. In this study, we report on the synthesis and evaluation of novel biodegradable poly(ε-caprolactone)-based MMCAs. Poly(α- propargyl-ε-caprolactone-co-ε-caprolactone)s containing 2, 5, and 10 mol % of propargyl groups have been prepared by ring-opening copolymerization of ε-caprolactone and the corresponding propargylated lactone. In parallel, a diazido derivative of the clinically used diethylenetriaminepentaacetic acid (DTPA)/Gd3+ complex has been synthesized. Finally, MRI-visible poly(ε-caprolactone)s (PCLs) were obtained by the efficient click ligation of these compounds via a CuI-catalyzed [3 + 2] cycloaddition. ICP-MS analyses confirmed the efficient coupling of the complex on the PCL backbone with the MRI-visible PCLs containing 1.0, 2.6, and 3.6 wt % of Gd3+. The influence of the Gd3+ grafting density on the T1 relaxation times and on the MRI visibility of the novel biodegradable MMCAs was evaluated. Finally, their stability and cytocompatibility were assessed with regard to their potential as innovative MRI-visible biomaterials for biomedical applications.
Pillar[5]arene as a Co-factor in templating rotaxane formation
Ke, Chenfeng,Strutt, Nathan L.,Li, Hao,Hou, Xisen,Hartlieb, Karel J.,McGonigal, Paul R.,Ma, Zhidong,Iehl, Julien,Stern, Charlotte L.,Cheng, Chuyang,Zhu, Zhixue,Vermeulen, Nicolaas A.,Meade, Thomas J.,Botros, Youssry Y.,Stoddart, J. Fraser
, p. 17019 - 17030 (2013)
After the manner in which coenzymes often participate in the binding of substrates in the active sites of enzymes, pillar[5]arene, a macrocycle containing five hydroquinone rings linked through their para positions by methylene bridges, modifies the binding properties of cucurbit[6]uril, such that the latter templates azide-alkyne cycloadditions that do not occur in the presence of only the cucurbit[6]uril, a macrocycle composed of six glycoluril residues doubly linked through their nitrogen atoms to each other by methylene groups. Here, we describe how a combination of pillar[5]arene and cucurbit[6]uril interacts cooperatively with bipyridinium dications substituted on their nitrogen atoms with 2-azidoethyl- to 5-azidopentyl moieties to afford, as a result of orthogonal templation, two [4]rotaxanes and one [5]rotaxane in >90% yields inside 2 h at 55 C in acetonitrile. Since the hydroxyl groups on pillar[5]arene and the carbonyl groups on cucurbit[6]uril form hydrogen bonds readily, these two macrocycles work together in a cooperative fashion to the extent that the four conformational isomers of pillar[5]arene can be trapped on the dumbbell components of the [4]rotaxanes. In the case of the [5]rotaxane, it is possible to isolate a compound containing two pillar[5]arene rings with local C5 symmetries. In addition to fixing the stereochemistries of the pillar[5]arene rings, the regiochemistries associated with the 1,3-dipolar cycloadditions have been extended in their constitutional scope. Under mild conditions, orthogonal recognition motifs have been shown to lead to templation with positive cooperativity that is fast and all but quantitative, as well as being green and efficient.
A Novel Estrogen Receptor α-Targeted Near-Infrared Fluorescent Probe for in Vivo Detection of Breast Tumor
Tang, Chu,Du, Yang,Liang, Qian,Cheng, Zhen,Tian, Jie
, p. 4702 - 4709 (2018)
The ability to detect breast cancer early in its progression is essential to improve patient survival and quality of life. The noninvasive and dynamic imaging and functional assessments of estrogen receptor-alpha (ERα), which is commonly expressed at high levels in breast cancer, are important for effective diagnosis and treatment. Hence, the development of a specific ERα-targeted probe is a major research goal. To that end, in the present study, we created a novel near-infrared (NIR) fluorescent probe, IRDye800CW-E2, for targeted ERα imaging in breast-tumor-bearing mice. IRDye800CW-E2 consisted of a cyanine dye IRDye800CW as the NIR fluorophore and the E2 analogue ethinyl estradiol amine as an ERα targeting ligand. The ethinyl estradiol amine was initially labeled with fluorescein isothiocyanate (FITC) to evaluate the binding specificity to human breast-tumor cells in vitro. Flow chamber and in vitro confocal laser endomicroscopy imaging experiments demonstrated that FITC-E2 was specifically taken up by MCF-7 cells. Furthermore, NIR fluorescence imaging revealed the ability of IRDye800CW-E2 to rapidly target tumors and to achieve good contrast between tumors and background signal 4-48 h postinjection. The fluorescent signal of IRDye800CW-E2 in tumors was successfully blocked by the coinjection of the endogenous ERα-ligand 17β-estradiol (E2) and the probe. Ex vivo fluorescent imaging further confirmed high uptake of the probe by tumors. These results indicated that IRDye800CW-E2 has great potential as an ERα-targeted imaging probe for early breast-tumor detection and has potential for clinical translation.
Modular Toolkit of Multifunctional Block Copoly(2-oxazoline)s for the Synthesis of Nanoparticles
Keckeis, Philipp,Zeller, Enriko,Jung, Carina,Besirske, Patricia,Kirner, Felizitas,Ruiz-Agudo, Cristina,Schlaad, Helmut,C?lfen, Helmut
supporting information, p. 8283 - 8287 (2021/05/07)
Post-polymerization modification provides an elegant way to introduce chemical functionalities onto macromolecules to produce tailor-made materials with superior properties. This concept was adapted to well-defined block copolymers of the poly(2-oxazoline) family and demonstrated the large potential of these macromolecules as universal toolkit for numerous applications. Triblock copolymers with separated water-soluble, alkyne- and alkene-containing segments were synthesized and orthogonally modified with various low-molecular weight functional molecules by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and thiol-ene (TE) click reactions, respectively. Representative toolkit polymers were used for the synthesis of gold, iron oxide and silica nanoparticles.
Development of Covalent, Clickable Probes for Adenosine A1and A3Receptors
Trinh, Phuc N. H.,Chong, Daniel J. W.,Leach, Katie,Hill, Stephen J.,Tyndall, Joel D. A.,May, Lauren T.,Vernall, Andrea J.,Gregory, Karen J.
supporting information, p. 8161 - 8178 (2021/06/30)
Adenosine receptors are attractive therapeutic targets for multiple conditions, including ischemia-reperfusion injury and neuropathic pain. Adenosine receptor drug discovery efforts would be facilitated by the development of appropriate tools to assist in target validation and direct receptor visualization in different native environments. We report the development of the first bifunctional (chemoreactive and clickable) ligands for the adenosine A1receptor (A1R) and adenosine A3receptor (A3R) based on an orthosteric antagonist xanthine-based scaffold and on an existing structure-activity relationship. Bifunctional ligands were functional antagonists with nanomolar affinity and irreversible binding at the A1R and A3R. In-depth pharmacological profiling of these bifunctional ligands showed moderate selectivity over A2Aand A2Badenosine receptors. Once bound to the receptor, ligands were successfully “clicked” with a cyanine-5 fluorophore containing the complementary “click” partner, enabling receptor detection. These bifunctional ligands are expected to aid in the understanding of A1R and A3R localization and trafficking in native cells and living systems.
INTRACELLULAR DELIVERY VEHICLE
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Paragraph 0166-0167, (2020/08/13)
PROBLEM TO BE SOLVED: To provide a vehicle which can easily deliver a desired component or compound into a cell without preventing cell proliferation. SOLUTION: A intracellular delivery vehicle has its surface covered with positive electric charge. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
