- Cationic poly(ester amide) dendrimers: Alluring materials for biomedical applications
-
Novel cationic poly(ester amide) dendrimers have been synthesized by copper(i) azide-alkyne cycloaddition (CuAAC) of a tripropargylamine core and azide-terminated dendrons, in turn prepared by iterative amide coupling of the new monomer 2,2′-bis(glycyloxymethyl)propionic acid (bis-GMPA). The alternation of ester and amide groups provided a dendritic scaffold that was totally biocompatible and degradable in aqueous media at physiological and acidic pH. The tripodal dendrimers naturally formed rounded aggregates with a drug that exhibited low water solubility, camptothecin, thus improving its cell viability and anti-Hepatitis C virus (anti-HCV) activity. The presence of numerous peripheral cationic groups enabled these dendrimers to form dendriplexes with both pDNA and siRNA and they showed effective in vitro siRNA transfection in tumoral and non-tumoral cell lines.
- Lancelot, Alexandre,González-Pastor, Rebeca,Clavería-Gimeno, Rafael,Romero, Pilar,Abian, Olga,Martín-Duque, Pilar,Serrano, José L.,Sierra, Teresa
-
-
Read Online
- Luminescence modulations of rhenium tricarbonyl complexes induced by structural variations
-
Octahedral d6 low-spin Re(I) tricarbonyl complexes are of considerable interest as noninvasive imaging probes and have been deeply studied owing to their biological stability, low toxicity, large Stokes shifts, and long luminescence lifetimes. We reported recently the bimodal IR and luminescence imaging of a Re(I) tricarbonyl complex with a Pyta ligand (4-(2-pyridyl)-1,2,3-triazole) in cells and labeled such metal-carbonyl complexes SCoMPIs for single-core multimodal probes for imaging. Re(I) tricarbonyl complexes have unique photophysical properties allowing for their unequivocal detection in cells but also present some weaknesses such as a very low luminescence quantum yield in aqueous medium. Further optimizations would thus be desirable. We therefore developed new Re(I) tricarbonyl complexes prepared from different ancillary ligands. Complexes with benzothiadiazole- triazole ligands show interesting luminescent quantum yields in acetonitrile and may constitute valuable luminescent metal complexes in organic media. A series of complexes with bidentate 1-(2-quinolinyl)-1,2,3-triazole (Taquin) and 1-(2-pyridyl)-1,2,3-triazole (Tapy) ligands bearing various 4-substituted alkyl side chains has been designed and synthesized with efficient procedures. Their photophysical properties have been characterized in acetonitrile and in a H 2O/DMSO (98/2) mixture and compared with those of the parent Quinta- and Pyta-based complexes. Tapy complexes bearing long alkyl chains show impressive enhancement of their luminescent properties relative to the parent Pyta complex. Theoretical calculations have been performed to further characterize this new class of rhenium tricarbonyl complexes. Preliminary cellular imaging studies in MDA-MB231 breast cancer cells reveal a strong increase in the luminescence signal in cells incubated with the Tapy complex substituted with a C12 alkyl chain. This study points out the interesting potential of the Tapy ligand in coordination chemistry, which has been so far underexploited.
- Bertrand, Helene C.,Clede, Sylvain,Guillot, Regis,Lambert, Francois,Policar, Clotilde
-
-
Read Online
- Semisynthesis of Chondroitin Sulfate e Tetrasaccharide from Hyaluronic Acid
-
Chondroitin sulfate (CS) is crucial glycosaminoglycan that regulates key functions of the nervous system. CS-E is one of the key CS subtypes that modulates the biological function of CS. Herein, N-protecting-group-free semisynthesis of CS-E tetrasaccharid
- Yao, Wang,Zhu, Yong,Zhang, Xiao,Sha, Meng,Meng, Xiangbao,Li, Zhongjun
-
-
Read Online
- One-pot tandem living radical polymerisation-Huisgens cycloaddition process ("click") catalysed by N-alkyl-2-pyridylmethanimine/Cu(I)Br complexes
-
Azide terminally functional poly(methyl methacrylate)s (Mn = 4000-6000, PDI = 1.21-1.28) have been prepared by living radical polymerization and successfully reacted with alkynes in a Huisgen cycloaddition (click) reaction in one pot using the same catalyst for both processes. The Royal Society of Chemistry 2005.
- Mantovani, Giuseppe,Ladmiral, Vincent,Tao, Lei,Haddleton, David M.
-
-
Read Online
- Synthesis of a novel polymeric material folate-poly(2-ethyl-2-oxazoline)- distearoyl phosphatidyl ethanolamine tri-block polymer for dual receptor and pH-sensitive targeting liposome
-
The in vivo distribution of antitumor drugs is usually lack of selectivity, and thus, leading to a low efficacy of chemotherapy on cancers and high toxicity to normal cells. Receptor-mediated targeting liposome with pH-sensitivity as a dual drug delivery
- Xia, Gui Min,An, Zhi Jiao,Wang, Yang,Zhao, Chen,Li, Mei,Li, Zi Chen,Ma, Jie
-
-
Read Online
- Competitive Affinity Release for Long-Term Delivery of Antibodies from Hydrogels
-
With increased clinical use of antibodies, long-term delivery strategies are needed to decrease injection frequency and improve health outcomes. A three-component drug-delivery system was developed for competitive affinity release of a streptavidin–antibody conjugate from agarose–desthiobiotin hydrogels via controlled dissolution of sparingly soluble biotin derivatives. The antibody conjugate was localized in the hydrogel through streptavidin–desthiobiotin complexation. Dissolution of sparingly soluble biotin derivatives disrupts streptavidin–desthiobiotin complexation for controlled release of the antibody conjugate. Release was tuned by altering the total biotin derivative concentration without further hydrogel or antibody modification. First-order tunable release of bioactive Avastin, a therapeutic anti-VEGF antibody, was demonstrated from a non-cytotoxic system for over 100 days.
- Huynh, Vincent,Wylie, Ryan G.
-
-
Read Online
- Efficient click chemistry towards fatty acids containing 1,2,3-triazole: Design and synthesis as potential antifungal drugs for Candida albicans
-
Candida is an important opportunistic human fungal pathogen. The cis-2-dodecenoic acid (BDSF) showing in vitro activity of against C. albicans growth, germ-tube germination and biofilm formation has been a potential inhibitor for Candida and other fungi.
- Fu, Nina,Wang, Suiliang,Zhang, Yuqian,Zhang, Caixia,Yang, Dongliang,Weng, Lixing,Zhao, Baomin,Wang, Lianhui
-
-
Read Online
- Facile Synthesis of Sequence-Regulated Synthetic Polymers Using Orthogonal SuFEx and CuAAC Click Reactions
-
The orthogonal sulfur–fluoride exchange reaction (SuFEx) and copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) are employed to synthesize sequence-regulated synthetic polymers. The high efficiency and broad tolerance of SuFEx and CuAAC to diverse chemical functionalities enable the one-pot synthesis of polydispersed sequence-controlled polymers by step-growth copolymerization in high yield and sequence complexity. Furthermore, iterative SuFEx and CuAAC coupling reactions on a solid support, without the need of protecting groups, afford monodispersed sequence-defined oligomers. The use of this orthogonal pair of click reactions provides new opportunities to facilely access sequence-regulated synthetic polymers with a high degree of structural diversity.
- Yang, Cangjie,Flynn, James P.,Niu, Jia
-
-
Read Online
- Macrocyclic polyamine [12]aneN3modified triphenylamine-pyrazine derivatives as efficient non-viral gene vectors with AIE and two-photon imaging properties
-
With the aim to develop a novel multifunctional gene delivery system that may overcome the common barriers of gene transfection, near-infrared fluorescent triphenylamine-pyrazine was modified with a DNA condensing triazole-[12]aneN3moiety through different length alkyl ester linkages to afford three new non-viral gene vectors,TDM-A/B/C. All compounds showed prominent solvatochromic fluorescence (Stokes shift of up to 383 nm) and two-photon absorption properties (σ2P to 101 GM), and exhibited strong aggregation-induced emission (AIE). Gel electrophoresis demonstrated that plasmid DNA was completely condensed at a concentration of 10 μM (TDM-A), 14 μM (TDM-B) and 16 μM (TDM-C), and released in esterase and acidic environment. SEM demonstrated that the three compounds were able to self-assemble and co-aggregate with DNA to form regular nanoparticles. Experiments demonstrated thatTDM-A/B/Cwas able to integrate with DNA through electrostatic interactions and supramolecular stacking, and the short alkyl linkage favored the strong interaction with DNA. Among the three compounds,TDM-Bshowed the best luciferase and GFP transfection activities in the presence of DOPE, which were 156% and 310% higher than those of Lipo2000, respectively. The transfection process of DNA was clearly traced through one- and two-photon fluorescence microscopy imaging. Cellular uptake inhibition assay indicated that the DNA complex entered the cell mainlyviaclathrin-independent endocytosis. Furthermore, thein vivotransfection experiments ofTDM-B/DOPE were successfully implemented in zebra fish embryos, and the GFP gene expression level was superior to that of Lipo2000 (200%). Finally, this study clearly unraveled that the length of the alkyl linkage affected the DNA condensation and transfection activity, which can serve as a base for the future rational design of non-viral gene vectors.
- Gao, Yong-Guang,He, Lan,Liu, Ming-Xuan,Liu, Xu-Ying,Lu, Zhong-Lin,Ma, Le-Le,Sun, Wan
-
-
Read Online
- Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners
-
3β-Azidocholest-5-ene (3) and (3β)-3-(prop-2-yn-1-yloxy)cholest-5-ene (10) were prepared as substrates to synthesize a variety of three-motif pharmacophoric conjugates through CuAAC. Basically, these conjugates included cholesterol and 1,2,3-triazole moie
- El Sayed Aly, Mohamed Ramadan,Saad, Hosam Ali,Abdel-Hafez, Shams Hashim
-
-
Read Online
- Intracellular location matters: Rationalization of the anti-inflammatory activity of a manganese(ii) superoxide dismutase mimic complex
-
A conjugate of a Mn-based superoxide dismutase mimic with a Re-based multimodal probe 1 was studied in a cellular model of oxidative stress. Its speciation was investigated using Re and Mn X-fluorescence. Interestingly, 1 shows a distribution different fr
- Bernard, Anne-Sophie,Delsuc, Nicolas,Henry, Lucas,Iriart, Sébastien,Ivanovi?-Burmazovi?, Ivana,Lai, Barry,Lung-Soong, Caroline,Marco, Sergio,Mathieu, Emilie,Medjoubi, Kadda,Nagarajan, Sounderya,Policar, Clotilde,Poyer, Florent,Quévrain, Elodie,Scheitler, Andreas,Seksik, Philippe,Somogyi, Andrea,Zoumpoulaki, Martha
-
-
Read Online
- Selective Uptake of Cylindrical Poly(2-Oxazoline) Brush-AntiDEC205 Antibody-OVA Antigen Conjugates into DEC-Positive Dendritic Cells and Subsequent T-Cell Activation
-
To achieve specific cell targeting by various receptors for oligosaccharides or antibodies, a carrier must not be taken up by any of the very many different cells and needs functional groups prone to clean conjugation chemistry to derive well-defined stru
- Bühler, Jasmin,Gietzen, Sabine,Reuter, Anika,Kappel, Cinja,Fischer, Karl,Decker, Sandra,Sch?ffel, David,Koynov, Kaloian,Bros, Matthias,Tubbe, Ingrid,Grabbe, Stephan,Schmidt, Manfred
-
-
Read Online
- Modular Toolkit of Multifunctional Block Copoly(2-oxazoline)s for the Synthesis of Nanoparticles
-
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.
- Keckeis, Philipp,Zeller, Enriko,Jung, Carina,Besirske, Patricia,Kirner, Felizitas,Ruiz-Agudo, Cristina,Schlaad, Helmut,C?lfen, Helmut
-
-
Read Online
- Europium confined cyclen dendrimers with photophysically active triazoles
-
Dendrimers up to the fourth generation (G1-G4) were successfully synthesized via the efficient copper catalyzed 1,3-dipolar cycloaddition between primary alkynes and azides (CuAAC), also referred to as a click reaction. The synthetic protocol involved the preparation of presynthesized dendron wedges that subsequently were attached to a tetra-valent alkyne functional cyclen core. These constructed structures integrated stable triazole groups "intra-locked" between the cyclen and dendron wedges. The incorporation of a lanthanide metal ion, europium, into the interior of all cyclen dendrimers was monitored by FT-IR. Interestingly, the photophysical results showed that the proximate triazole not only acts as a stable linker but also as a sensitizers, transferring its singlet-singlet excitation in the ultraviolet region (270-290 nm) to the partially filled luminescent lanthanide 4f shell. An increase of luminescence decay time from the lanthanide 5D0 → 7F2 emission was observed with increasing dendrimer size, indicating that the shielding effect of the dendron wedges is important for the relaxation of the photo-excitation and energy transfer. To the best of our knowledge, this is the first time a set of dendron wedges have successfully been attached to a cyclen metal ion cage via the versatile click reaction. Furthermore, the produced triazoles intra-locked in close proximity to the macrocycle core elucidated an interesting photophysical function.
- Antoni, Per,Malkoch, Michael,Vamvounis, George,Nystroem, Daniel,Nystroem, Andreas,Lindgren, Mikael,Hult, Anders
-
-
Read Online
- Activity-based protein profiling in vivo using a copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition
-
Toward the goal of assigning function to the tens of thousands of protein products encoded by eukaryotic and prokaryotic genomes, the field of proteomics requires new technologies that can functionally characterize proteins within the dynamic environment
- Speers, Anna E.,Adam, Gregory C.,Cravatt, Benjamin F.
-
-
Read Online
- Anionic Polymerization of Azidoalkyl Glycidyl Ethers and Post-Polymerization Modification
-
Polyethers like poly(ethylene glycol) have been widely used for a variety of valuable applications, although their functionalization still poses challenges due to the absence of functional handles along the polymer backbone. Herein, a series of novel azide-functionalized glycidyl ether monomers are presented as a universal approach to synthesize functional polyethers by post-polymerization modification. Three azide-functionalized glycidyl ether monomers possessing different alkyl spacers (ethyl, butyl, and hexyl) were designed and synthesized by a simple two-step substitution reaction. Organic superbase-catalyzed anionic ring-opening polymerization can proceed under mild conditions compatible with an azide pendant group, affording well-controlled azide-functionalized polyethers with low dispersity (? 1.2). The azide pendant groups on the resulting polymers were readily modified to a variety of functional groups via copper-catalyzed azide-alkyne cycloaddition reactions and Staudinger reduction. Furthermore, copolymerization of azidohexyl glycidyl ether with allyl glycidyl ether was demonstrated to provide an additional orthogonal functional handle. We anticipate that this work provides a new platform for the preparation of diverse functional polyethers.
- Lee, Joonhee,Han, Sohee,Kim, Minseong,Kim, Byeong-Su
-
-
Read Online
- Structurally diverse dendritic libraries: A highly efficient functionalization approach using click chemistry
-
The high fidelity and efficiency of Click chemistry are exploited in the synthesis of a library of chain end functionalized dendritic macromolecules. In this example, the selectivity of the Cu-catalyzed [3 + 2π] cycloaddition reaction of azides with termi
- Malkoch, Michael,Schleicher, Kristin,Drockenmuller, Eric,Hawker, Craig J.,Russell, Thomas P.,Wu, Peng,Fokin, Valery V.
-
-
Read Online
- A safe and convenient method for the preparation of triflyl azide, and its use in diazo transfer reactions to primary amines
-
A safe and convenient method for the copper(II)-catalyzed diazo transfer from triflyl azide to primary amines is reported. By replacing CH2Cl2 by toluene the formation of hazardous side products, for example, azido-chloromethane and diazidomethane can be avoided.
- Titz, Alexander,Radic, Zorana,Schwardt, Oliver,Ernst, Beat
-
-
Read Online
- A new homobifunctional p-nitro phenyl ester coupling reagent for the preparation of neoglycoproteins
-
(Chemical equation presented) A new linker system has been designed and applied to neoglycoprotein synthesis. Reaction of oligosaccharide ω-aminoalkyl glycosides with homobifunctional adipic acid p-nitrophenyl diesters in dry DMF gave the corresponding am
- Wu, Xiangyang,Ling, Chang-Chun,Bundle, David R.
-
-
Read Online
- Discovery of human hexosaminidase inhibitors by in situ screening of a library of mono- and divalent pyrrolidine iminosugars
-
Two libraries of mono- and dimeric pyrrolidine iminosugars were synthesized by CuAAC and (thio)urea-bond-forming reactions from the respective azido/aminohexylpyrrolidine iminosugar precursors. The resulting monomeric and dimeric compounds were screened f
- Bojarová, Pavla,Carmona, Ana T.,K?en, Vladimír,Kulik, Natalia,Mészáros, Zuzana,Martínez-Bailén, Macarena,Moreno-Vargas, Antonio J.,Pingitore, Valeria,Robina, Inmaculada,Slámová, Kristyna
-
supporting information
(2022/02/14)
-
- A metal-free reductive N-alkylation of indoles with aldehydes
-
A simple metal-free method has been developed for the reductive N-alkylation of indoles employing aldehydes as the alkylating agent and inexpensive Et3SiH as the reductant. A wide range of aromatic and aliphatic aldehydes are viable substrates along with
- Clanton, Nicholas A.,Spiller, Taylor E.,Ortiz, Eliezer,Gao, Zhinong,Rodriguez-Poirier, Juan Manuel,Delmonte, Albert J.,Frantz, Doug E.
-
p. 3233 - 3236
(2021/04/05)
-
- Design, synthesis and antiparasitic evaluation of click phospholipids
-
A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against Leishmania infantum and Leishmania donovani intracellular amastigotes, against Trypanosoma brucei brucei and against different developmental stages of Trypanosoma cruzi. The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure–activity relationships. The early ADMET profile of the new derivatives did not reveal major liabilities for the potent compounds. The 1,2,3-triazole derivative 27 substituted by a decyl tail, an undecyl spacer and a choline head group exhibited broad spectrum antiparasitic activity. It possessed low micromolar activity against the intracellular amastigotes of two L. infantum strains and T. cruzi Y strain epimastigotes, intracellular amastigotes and trypomastigotes, while its cytotoxicity concentration (CC50) against THP-1 macrophages ranged between 50 and 100 μM. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases.
- Afroudakis, Pantelis,Barrias, Emile,Bifeld, Eugenia,Borsari, Chiara,Calogeropoulou, Theodora,Clos, Joachim,Costi, Maria Paola,Ellinger, Bernhard,Fotopoulou, Theano,Fragiadaki, Irini,Georgikopoulou, Kalliopi,Gul, Sheraz,Hachenberg, Julia,Kuzikov, Maria,Magoulas, George E.,Prousis, Kyriakos C.,Roussaki, Marina,Santarem, Nuno,Scoulica, Effie,Tejera Nevado, Paloma,da Silva, Anabela Cordeiro,de Souza, Wanderley
-
-
- PROTEIN-MACROMOLECULE CONJUGATES AND METHODS OF USE THEREOF
-
The present disclosure provides protein-macromolecule conjugates, releasable linkers, and macromolecules, as defined herein. The disclosed conjugates provide unique properties that are based at least upon the properties of linker and number of linker-Macromolecule moieties. Also provided herein are a method of synthesis and use of conjugates in treating diseases and disorders.
- -
-
Paragraph 0384-0385
(2021/04/10)
-
- Manganese=Catalyzed Achmatowicz Rearrangement Using Green Oxidant H2O2
-
Oxidation reactions have been extensively studied in the context of the transformations of biomass=derived furans. However, in contrast to the vast literature on utilizing the stoichiometric oxidants, such as m=CPBA and NBS, catalytic methods for the oxidative furan=recyclizations remain scarcely investigated. Given this, we report a means of manganese=catalyzed oxidations of furan with low loading, achieving the Achmatowicz rearrangement in the presence of hydrogen peroxide as an environmentally benign oxidant under mild conditions with wide functional group compatibility.
- Xing, Qingzhao,Hao, Zhe,Hou, Jing,Li, Gaoqiang,Gao, Ziwei,Gou, Jing,Li, Chaoqun,Yu, Binxun
-
p. 9563 - 9586
(2021/07/20)
-
- Synthesis of the Fungal Metabolite YWA1 and Related Constructs as Tools to Study MelLec-Mediated Immune Response to Aspergillus Infections ?
-
We describe the chemical synthesis of the fungal naphthopyrones YWA1 and fonsecin B, as well as their functionalization with an amine-spacer arm and the conjugation of the resulting molecules to three different functional tags (i.e., biotin, Oregon green, 1-[3-(succinimidyloxycarbonyl)benzyl]-4-[5-(4-methoxyphenyl)-2-oxazolyl]pyridinium bromide (PyMPO)). The naphthopyrone-biotin and -PyMPO constructs maintained the ability to bind the C-type lectin receptor MelLec, whose interaction with immunologically active fungal metabolites (i.e., 1,8-dihydroxynaphthalene-(DHN)-melanin and YWA1) is a key step in host recognition and induction of protective immune responses against Aspergillus fumigatus. The fluorescent Fonsecin B-PyMPO construct 21 was used to selectively visualize MelLec-expressing cells, thus validating the potential of this strategy for studying the role and functions of MelLec in immunity.
- Piras, Monica,Patruno, Ilaria,Nikolakopoulou, Christina,Willment, Janet A.,Sloan, Nikki L.,Zanato, Chiara,Brown, Gordon D.,Zanda, Matteo
-
p. 6044 - 6055
(2021/05/29)
-
- Magnetic Resonance Imaging of PSMA-Positive Prostate Cancer by a Targeted and Activatable Gd(III) MR Contrast Agent
-
Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed in aggressive prostate cancer (PCa) and has been extensively studied as a PCa diagnostic imaging biomarker. Multiple imaging modalities have exploited PSMA as a
- Basilion, James P.,Li, Hao,Luo, Dong,Meade, Thomas J.,Wang, Jing,Wang, Xinning,Yuan, Chaonan
-
supporting information
p. 17097 - 17108
(2021/10/25)
-
- Ytterbium-Catalyzed Intramolecular [3 + 2] Cycloaddition based on Furan Dearomatization to Construct Fused Triazoles
-
The 1,2,3-triazole-containing polycyclic architecture widely exists in a broad spectrum of synthetic bioactive molecules, and the development of expeditious methods to synthesize these skeletons remains a challenging task. In this work, the catalytic cyclization of biomass-derived 2-furylcarbinols with an azide to form fused triazoles is described. This approach takes advantage of a single catalyst Yb(OTf)3 and operates via a furfuryl-cation-induced intramolecular [3 + 2] cycloaddition/furan ring-opening cascade.
- Xu, Xiaoming,Zhong, Ying,Xing, Qingzhao,Gao, Ziwei,Gou, Jing,Yu, Binxun
-
supporting information
p. 5176 - 5181
(2020/07/14)
-
- High-Yielding Water-Soluble Asymmetric Cyanine Dyes for Labeling Applications
-
A simple and efficient microwave-assisted synthesis of asymmetric pentamethine cyanine dyes with various functional groups was developed, which allows high-yielding results. The synthesized dyes are modifiable and suitable for single-molecule imaging in biological and medical sciences by application of click chemistry or classic esterification and amidation.
- Wolf, Natalia,Kersting, Louise,Herok, Christoph,Mihm, Cornelius,Seibel, Juergen
-
supporting information
p. 9751 - 9760
(2020/09/03)
-
- Peptide-like monomer as well as polymer and application thereof
-
The invention provides a peptide-like monomer as well as a polymer and an application thereof. The structural formula of the peptide-like monomer is shown in a formula I, wherein n is any integer of 1to 6; R is H, C1-C12 non-reactive alkyl or C1-C12 reactive alkyl, the C1-C12 non-reactive alkyl is linear or branched chain alkyl without active groups, the C1-C12 reactive alkyl is linear or branched chain alkyl containing active groups, and the active groups comprise at least one of hydroxyl, alkenyl, alkynyl, halogen and mercapto; the cyclic structure of the peptide-like monomer is oxygen-containing anhydride or sulfur-containing thioanhydride. The invention further provides a preparation method of the polymer of the peptide-like monomer and a preparation method of a modified polymer. Various clustering peptide polymers can be directly prepared from the peptide-like monomer through ring-opening polymerization, and the prepared functionalized clustering peptide polymer can be subjectedto various functional modification and is applied to the field of biomedical materials.
- -
-
Paragraph 0050-0054
(2019/07/04)
-
- Reactions of α-haloacroleins with azides: Highly regioselective synthesis of formyl triazoles
-
A general metal-free route to 1,4-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles was developed. α-Haloacroleins reacted with organic azides in a DMSO/H2O mixture solvent at room temperature to produce 1,4-disubstituted triazoles (up to 99%) with exclusive regioselectivities. This protocol is convenient and scalable with a broad substrate scope including aliphatic and aromatic azides. The resulting triazoles exhibited an aldehyde group at the C4 position and demonstrated synthetic utilizations. One 1,2,3-triazole compound containing diastereotopic protons was also identified.
- Zhang, Dongsheng,Fan, Yingzhu,Yan, Zhongliang,Nie, Yi,Xiong, Xingquan,Gao, Lizhu
-
supporting information
p. 4211 - 4216
(2019/08/07)
-
- Biological silver ion fluorescent probe containing triazole anthraquinone derivative and preparation method and application thereof
-
The invention discloses a biological silver ion fluorescent probe containing a triazole anthraquinone derivative and a preparation method and application thereof, and belongs to the technical fields of chemical analysis and biological analysis. The biological silver ion fluorescent probe containing the triazole anthraquinone derivative is technically characterized in that a structural formula is shown in the attached figure, wherein n is equal to 1 or 4. The invention specifically discloses the preparation method of the biological silver ion fluorescent probe containing the triazole anthraquinone derivative and application in selective detection and analysis of silver ions in water environment systems or biological cell systems. The prepared biological silver ion fluorescent probe containing the triazole anthraquinone derivative has good water solubility, biocompatibility and membrane permeability, the imaging of silver ions is realized in human liver cancer cells HepG2, and the potential application value is realized in detection of silver ions in actual biological samples.
- -
-
Paragraph 0036; 0037; 0041; 0042
(2018/12/13)
-
- Nonmigratory internal plasticization of poly(vinyl chloride) via pendant triazoles bearing alkyl or polyether esters
-
Branched and linear nonmigratory internal plasticizers attached to PVC by a pendant triazole linkage were synthesized and investigated. Copper-free azide-alkyne thermal cycloaddition was employed to covalently bind triazole-based phthalate mimics to PVC. To systematically investigate the effect of plasticizer structure on glass transition temperature, several architectural motifs were explored. Free volume theory was considered when designing many of these internal plasticizers: hexyl-tethers were utilized to generate additional space between the triazole-phthalate mimic and the polymer backbone. Miscibility of these triazole-plasticizers in PVC is important: variation of the ester moieties on the triazole possessing alkyl and/or poly(ethylene oxide) chains produced a wide range of glass transition temperatures (Tg): from anti-plasticizing 96 °C, to highly efficient plasticized materials exhibiting Tg values as low as ?42 °C.
- Higa, Chad M.,Tek, Andy T.,Wojtecki, Rudy J.,Braslau, Rebecca
-
p. 2397 - 2411
(2018/10/02)
-
- Addressable Cholesterol Analogs for Live Imaging of Cellular Membranes
-
Cholesterol is an essential component of most biological membranes and serves important functions in controlling membrane integrity, organization, and signaling. However, probes to follow the dynamic distribution of cholesterol in live cells are scarce and so far show only limited applicability. Herein, we addressed this problem by synthesizing and characterizing a class of versatile and clickable cholesterol-based imidazolium salts. We show that these cholesterol analogs faithfully mimic the biophysical properties of natural cholesterol in phospholipid mono- and bilayers, and that they integrate into the plasma membrane of cultured and primary human cells. The membrane-incorporated cholesterol analogs can be specifically labeled by click chemistry and visualized in live-cell imaging experiments that show a distribution and behavior comparable with that of endogenous membrane cholesterol. These results indicate that the cholesterol analogs can be used to reveal the dynamic distribution of cholesterol in live cells. Cholesterol is an important component of biological membranes, but probes recording its dynamic intracellular distribution are scarce. Rakers et al. developed cholesterol-derived imidazolium salts mimicking properties of natural cholesterol. Following specific labeling via click chemistry, one of the cholesterol analogs was shown to incorporate into cellular membranes equivalent to endogenous cholesterol.
- Rakers, Lena,Grill, David,Matos, Anna L.L.,Wulff, Stephanie,Wang, Da,B?rgel, Jonas,K?rsgen, Martin,Arlinghaus, Heinrich F.,Galla, Hans-Joachim,Gerke, Volker,Glorius, Frank
-
p. 952 - 12,961
(2018/05/08)
-
- Effect of Anomeric Configuration on Stereocontrolled α-Glycosylation of l -Fucose
-
In this letter, we report an approach to the stereoselective α-glycosylation of l -fucose that is exemplified by effect of anomeric configuration. The neighboring group participation is not compatible with α-glycosylation of l -fucose, therefore the remote participation by 4- O -Bz was employed to control the formation of 1,2- cis -glycosidic bond. Furthermore, we found the anomeric configuration of fucose donor is crucial to stereoselectivity of the glycosylated products. The α/β-mixed products were generated by using β-anomeric donor while the glycosyl donor in α configuration yielded products in high α-selectivity possibly due to the distinct pathway to forming the key intermediates. This phenomenon supplies the basis for the synthesis of complicated natural carbohydrates containing fucose α-glycoside, such as fucoidans, fucosylated N -glycans, and fucosylated chondroitin sulfates, etc.
- Wang, Lihao,Fan, Fei,Wu, Haotian,Gao, Lei,Zhang, Ping,Sun, Tiantian,Yang, Chendong,Yu, Guangli,Cai, Chao
-
supporting information
p. 2701 - 2706
(2018/12/13)
-
- Stereodivergent synthesis of right- and left-handed iminoxylitol heterodimers and monomers. Study of their impact on β-glucocerebrosidase activity
-
A library of dimers and heterodimers of both enantiomers of 2-O-alkylated iminoxylitol derivatives has been synthesised and evaluated on β-glucocerebrosidase (GCase), the enzyme responsible for Gaucher disease (GD). Although the objective was to target simultaneously the active site and a secondary binding site of the glucosidase, the (-)-2-iminoxylitol moiety seemed detrimental for imiglucerase inhibition and no significant enhancement was obtained in G202R, N370S and L444P fibroblasts. However, all compounds having at least one (+)-2-O-alkyl iminoxylitol are GCase inhibitors in the nano molar range and are significant GCase activity enhancers in G202R fibroblats, as confirmed by a decrease of glucosylceramide levels and by co-localization studies.
- Stauffert, Fabien,Serra-Vinardell, Jenny,Gómez-Grau, Marta,Michelakakis, Helen,Mavridou, Irene,Grinberg, Daniel,Vilageliu, Llu?sa,Casas, Josefina,Bodlenner, Anne,Delgado, Antonio,Compain, Philippe
-
supporting information
p. 3681 - 3705
(2017/07/07)
-
- HYDROGELS WITH BIODEGRADABLE CROSSLINKING
-
Hydrogels that degrade under appropriate conditions of pH and temperature by virtue of crosslinking compounds that cleave through an elimination reaction are described. The hydrogels may be used for delivery of various agents, such as pharmaceuticals.
- -
-
Paragraph 0161
(2017/11/16)
-
- METHOD FOR PREPARING 6-AMINOHEXYL LACTOSIDE-NOTA CONJUGATE
-
The present invention provides a method for preparing a 6-aminohexyl lactoside-NOTA conjugate. The preparation method comprises brominating perbenzoylated lactose with hydrobromic acid; glycosylating 6-azidohexanol to obtain 6-azidohexyl perbenzoyl lactoside; and deprotecting this precursor in two steps to obtain 6-aminohexyl lactoside and conjugating 6-aminohexyl lactoside to NCS-benzyl-NODA GA (i.e. 2,2′-(7-(1-carboxy-4-((4-isothiocyanate benzyl) amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl) diacetic acid) in triethyl amine as an alkaline solvent, to obtain a 6-aminohexyl lactoside-NCS-benzyl-NODA GA conjugate. In this novel preparation method, no deglycosylated side product is produced, such that the yield is considerably increased to 46%. Therefore, the method is suitable for future massive production since the requirement for repeated preparations for massive production is reduced, and the impurities produced in the previously scaled-up preparation process are not present.
- -
-
Paragraph 0052; 0053; 0054
(2017/07/14)
-
- MODIFIED NUCLEOTIDE REAGENTS
-
Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
- -
-
Paragraph 0238
(2017/11/29)
-
- Carboxylate-Assisted Iridium-Catalyzed C-H Amination of Arenes with Biologically Relevant Alkyl Azides
-
An iridium-catalyzed C-H amination of arenes with a wide substrate scope is reported. Benzamides with electron-donating and -withdrawing groups and linear, branched, and cyclic alkyl azides are all applicable. Cesium carboxylate is crucial for both reactivity and regioselectivity of the reactions. Many biologically relevant molecules, such as amino acid, peptide, steroid, sugar, and thymidine derivatives can be introduced to arenes with high yields and 100 % chiral retention. Ir responsible! A direct C-H amination between benzamide derivatives and various alkyl azides was achieved using iridium catalysis (see scheme; NTf=trifluoromethanesulfonyl amide). Cesium carboxylate was found to be the promoter and regiocontroller of this reaction. By this method, many biological active molecules can be introduced to benzamide components with high yields and 100 % chiral retention.
- Zhang, Tao,Hu, Xuejiao,Wang, Zhen,Yang, Tiantian,Sun, Hao,Li, Guigen,Lu, Hongjian
-
supporting information
p. 2920 - 2924
(2016/03/23)
-
- Site specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
-
The invention relates to compositions and methods for site-specific delivery of nucleic acids by combining them with targeting ligands and endosomolytic components.
- -
-
Page/Page column 139; 140; 141
(2016/06/13)
-
- Protein charge regulator and protein-encapsulating polymer micelle complex
-
The present invention provides a protein delivery means (e.g., a polyion complex) which allows efficient introduction into cells (particularly into the cytoplasm), is highly stable in serum, and is also widely applicable. The polyion complex of the present invention comprises a cationic polymer having a polycation moiety and a charge-conversional protein whose overall charge is converted from basic or neutral to acidic by a specific charge regulator.
- -
-
Page/Page column
(2015/06/16)
-
- Long-chain alkyltriazoles as antitumor agents: Synthesis, physicochemical properties, and biological and computational evaluation
-
A series of novel long-chain alkyltriazoles were prepared from commercial diols in a rapid process with good yields. The compounds were evaluated in vitro for their anticancer potential against two human cancer cell lines: colon carcinoma (RKO) and uterine carcinoma (HeLa). The results of colorimetric MTT assays showed that six of fourteen compounds tested decreased cell viability in these cell lines. Compounds 5e and 6a were the most active against RKO cells, with IC50 values of 16.70 and 14.57 μM, respectively. The same compounds, 5e and 6a, were the most active in HeLa cells as well, with IC50 values of 11.05 and 12.77 μM, respectively. In addition, compound 5e was found to induce apoptosis in RKO cells, as assessed by TUNEL assay. The results suggest that compound 5e may be a promising prototype anticancer agent.
- Gontijo, Vanessa Silva,Oliveira, Michael der,Resende, Rafael Jos,Fonseca, Amanda Luisa,Nunes, Renata Rachide,Jnior, Moacyr Comar,Taranto, Alex Gutterres,Torres, Natalia Machado Pereira Oliveira,Viana, Gustavo Henrique Ribeiro,Silva, Luciana Maria,Alves, Rosemeire Brondi,Varotti, Fernando Pilla,Freitas, Rossimiriam Pereira
-
p. 430 - 441
(2015/03/31)
-
- Protein and peptide-free synthetic vaccines against streptococcus pneumoniae type 3
-
The present invention provides a protein- and peptide-free conjugate comprising a synthetic carbohydrate and a carrier molecule, wherein the synthetic carbohydrate is a Streptococcus pneumoniae type 3 capsular polysaccharide related carbohydrate and the carrier molecule is a glycosphingolipid. Said conjugate and pharmaceutical composition thereof are useful for immunization against diseases associated with Streptococcus pneumoniae, and more specifically against diseases associated with Streptococcus pneumoniae type 3.
- -
-
-
- PROTEIN AND PEPTIDE-FREE SYNTHETIC VACCINES AGAINST STREPTOCOCCUS PNEUMONIAE TYPE 3
-
The present invention provides a protein- and peptide-free conjugate comprising a synthetic carbohydrate and a carrier molecule, wherein the synthetic carbohydrate is a Streptococcus pneumoniae type 3 capsular polysaccharide related carbohydrate and the carrier molecule is a glycosphingolipid. Said conjugate and pharmaceutical composition thereof are useful for immunization against diseases associated with Streptococcus pneumoniae, and more specifically against diseases associated with Streptococcus pneumoniae type 3.
- -
-
-
- Click reaction based synthesis, antimicrobial, and cytotoxic activities of new 1,2,3-triazoles
-
Three-motif pharmacophoric models 20a-e and 21-25 were prepared in good yields by CuAAC of two azido substrates 2 and 11 with seven terminal acetylenic derivatives including chalcones 17a-e, theophylline 18 and cholesterol 19. The structure of these compounds was elucidated by NMR, MS, IR spectroscopy and micro analyses. This series was screened as antimicrobial and cytotoxic agents in vitro. Most derivatives showed appreciable antibacterial activity, but they displayed weak cytotoxic, and antifungal activities. Notably, conjugate 25 (cream of the crop) was found to be more active than Ampicillin against Escherichia coli and Staphylococcus aureus and showed appreciable antifungal and cytotoxic activities as well.
- Syed Aly, Mohamed Ramadan El,Saad, Hosam Ali,Mohamed, Mosselhi Abdelnabi Mosselhi
-
p. 2824 - 2830
(2015/06/08)
-
- POLYSACCHARIDE ANTIGEN-GLYCOLIPID CONJUGATE VACCINES
-
The present invention relates to the field of synthesizing and biologically evaluating of a novel class of carbohydrate-based vaccines. The new vaccines consist of a multi-modular structure which allows applying the vaccine to a whole variety of pathogenes. This method allows preparing vaccines against all pathogens expressing immunogenic carbohydrate antigens. As conjugation of antigenic carbohydrates to proteins is not required the conjugate vaccine is particularly heat stable. No refrigeration is required, a major drawback of protein-based vaccines.
- -
-
-
- CARBOHYDRATE-GLYCOLIPID CONJUGATE VACCINES
-
The present invention relates to the field of synthesizing and biologically evaluating of a novel class of carbohydrate-based vaccines. The new vaccines consist of a multi-modular structure which allows applying the vaccine to a whole variety of pathogenes. This method allows preparing vaccines against all pathogens expressing immunogenic carbohydrate antigens. As conjugation of antigenic carbohydrates to proteins is not required the conjugate vaccine is particularly heat stable. No refrigeration is required, a major drawback of protein-based vaccines.
- -
-
-
- SLOW-RELEASE CONJUGATES OF SN-38
-
Conjugates of SN-38 that provide optimal drug release rates and minimize the formation of the corresponding glucuronate are described. The conjugates release SN-38 from a polyethylene glycol through a β-elimination mechanism.
- -
-
Paragraph 0055
(2015/04/22)
-
- Self-assembling amphiphilic Janus dendrimers: Mesomorphic properties and aggregation in water
-
The self-assembly behaviour both in bulk and in water of amphiphilic dendrimeric derivatives based on bis-MPA is the central theme of this article. The designed molecules possess two parts with different polarity; this feature is the key factor that forces their self-assembly in water into supramolecular architectures, due to hydrophobic interactions between the lipophilic fractions of the molecules, and the appearance of mesomorphic order in bulk in response to a variation of temperature (thermotropic liquid crystals). The effects provoked by the hydrophilic/lipophilic balance of the molecule were studied varying the generation of the corresponding dendrons and combining them via CuAAC click chemistry in order to obtain symmetrical and unsymmetrical final Janus dendrimers. The ability of the aggregates formed in water to encapsulate hydrophobic drugs has also been explored.
- Fedeli, Elisabetta,Lancelot, Alexandre,Serrano, José Luis,Calvo, Pilar,Sierra, Teresa
-
supporting information
p. 1960 - 1967
(2015/03/18)
-
- NOVEL SEMI-SYNTHETIC MENINGOCOCCAL CONJUGATE VACCINE
-
The present invention relates to novel semi-synthetic meningococcal conjugate vaccine comprising novel synthetic oligosaccharide conjugated to a carrier protein. The present invention also relates to novel synthetic meningococcal oligosaccharide and a process for its preparation.
- -
-
Page/Page column 22
(2016/03/04)
-
- Reactions in elastomeric nanoreactors reveal the role of force on the kinetics of the Huisgen reaction on surfaces
-
The force dependence of the copper-free Huisgen cycloaddition between an alkyne and a surface-bound azide was examined in elastomeric nanoreactors. These studies revealed that pressure and chain length are critical factors that determine the reaction rate. These experiments demonstrate the central role of pressure and surface structure on interfacial processes that are increasingly important in biology, materials science, and nanotechnology.
- Han, Xu,Bian, Shudan,Liang, Yong,Houk,Braunschweig, Adam B.
-
supporting information
p. 10553 - 10556
(2014/08/18)
-
- Synthesis and immunological characterization of modified hyaluronic acid hexasaccharide conjugates
-
The synthesis of a tetanus toxoid (TT)-conjugate of a hyaluronic acid (HA) hexasaccharide is described. The compound was intended for use in monitoring HA levels as a disease marker and as a potential vaccine against Group A Streptococcus (GAS) infections. We also report the synthesis of a chemically modified HA-hexasaccharide-TT conjugate in which the N-acetyl moiety of the N-acetyl-d-glucosamine residue is replaced with an N-propionyl unit in order to enhance immunogenicity. The oligosaccharides are synthesized in a convergent manner. The TT-conjugate syntheses rely on the reaction of the amines on the 6-aminohexyl aglycon of the hexasaccharides with diethyl squarate to give the monoethyl squarate adducts. Subsequent reactions with lysine ε-amino groups on TT then give the glycoconjugates containing an average of 8 hexasaccharide haptens per TT molecule. Immunological studies in mice show very similar antibody responses with both conjugates, suggesting that the N-acetyl groups of the glucosaminyl residues of the HA-hexasaccharide are not a critical part of the epitope recognized by the anti-HA polyclonal immune response. Furthermore, it would appear that the N-acyl moieties are not in close contact with the amino acid residues of the antibody combining sites.
- Gu, Guofeng,Adabala, Pal John Pal,Szczepina, Monica G.,Borrelli, Silvia,Pinto, B. Mario
-
p. 8004 - 8019
(2013/09/12)
-
- Rapid synthesis of oligomannosides with orthogonally protected monosaccharides
-
We developed a facile synthesis to yield orthogonally protected mannose building blocks with high overall yields. The protection/glycosylation steps can be carried out in a successive manner without purification of intermediate products. This developed synthesis led to formation of linear/branched tri-, penta- and heptasaccharides.
- Chang, Sue-Ming,Tu, Zhijay,Jan, Hau-Ming,Pan, Jia-Fu,Lin, Chun-Hung
-
supporting information
p. 4265 - 4267
(2013/05/22)
-
- SULFONE LINKERS
-
Sulfone linkers which couple drugs to carriers of various types are described. These linkers permit the release of the drug over time in a controlled manner. The release occurs through beta-elimination, and does not require enzymatic cleavage. Products of
- -
-
Paragraph 0064
(2013/03/26)
-
- HYDROGELS WITH BIODEGRADABLE CROSSLINKING
-
Hydrogels that degrade under appropriate conditions of pH and temperature by virtue of crosslinking compounds that cleave through an elimination reaction are described. The hydrogels may be used for delivery of various agents, such as pharmaceuticals. Thi
- -
-
Paragraph 0094
(2013/03/26)
-
- Click chemistry based synthesis of dopamine D4 selective receptor ligands for the selection of potential PET tracers
-
Taking advantage of click chemistry, a library of N-arylpiperazinylmethyl triazoles bearing fluoro substituted appendages was synthesized and the target compounds were investigated for dopamine and serotonin receptor binding. With the aim to bias their hydrophilicity and to optimize their D4 receptor affinity and selectivity, a concise series of triazoles containing fluoroalkyl, fluoroalkoxy, fluoroalkoxyphenyl, and deoxyfluoroglucosyl substituents was studied. The D4 receptor affinity and selectivity could be tuned by altering the chemical moiety attached to the triazole unit. Among the test compounds, the fluoroethoxyphenyl derivative 15b showed weak partial agonism at D4 and a K i value of 14 nM, while its fluoropropoxyphenyl homologue 16a turned out to act as a neutral D4 antagonist (Ki = 5.1 nM). Both, 15b and 16a revealed an excellent balance between D4 receptor affinity and subtype selectivity, providing lead candidates for the development of 18F-labeled radioligands for D4 receptor imaging studies by positron emission tomography (PET).
- Banerjee, Ashutosh,Maschauer, Simone,Hübner, Harald,Gmeiner, Peter,Prante, Olaf
-
p. 6079 - 6082
(2013/11/06)
-