Search results for "CLICK CHEMISTRY"

Multi-olefin containing polyethers and triazolinediones: a powerful alliance

2019

Multi-functional polyethers with ene or diene moieties were prepared via the polymerisation of tailored functional glycidyl ether monomers to create a platform for click chemistry with triazolinediones (TADs). Specifically, two novel monomers (i) 2,4-hexadien-1-yl glycidyl ether (HDEGE) and (ii) citronellyl glycidyl ether (CitroGE), designed to undergo a Diels–Alder or Alder–Ene reaction with TADs, respectively, were synthesized and subsequently transformed into a variety of tailored polyethers, either via the monomer activated method or anionic ring opening polymerisation. Multi-functional copolymers of HDEGE with ethylene oxide, propylene oxide and ethoxy ethyl glycidyl ether as well as A…

HPMA-Based Nanoparticles for Fast, Bioorthogonal iEDDA Ligation

2019

Contains fulltext : 216143.pdf (Publisher’s version ) (Open Access) Fast and bioorthogonally reacting nanoparticles are attractive tools for biomedical applications such as tumor pretargeting. In this study, we designed an amphiphilic block copolymer system based on HPMA using different strategies to introduce the highly reactive click units 1,2,4,5-tetrazines (Tz) either at the chain end (Tz-CTA) or statistical into the hydrophobic block. This reactive group undergoes a rapid, bioorthogonal inverse electron-demand Diels-Alder reaction (iEDDA) with trans-cyclooctenes (TCO). Subsequently, this polymer platform was used for the preparation of different Tz-covered nanoparticles, such as micell…

"A versatile post-polymerization modification method for polyglutamic acid: synthesis of orthogonal reactive polyglutamates and their use in ""click …

2013

In this article we describe a versatile methodology for the synthesis of polyglutamic acid (PGA) derivatives bearing orthogonal reactive sites. The reactive groups enable selective conjugation chemistry by copper catalyzed azide-alkyne coupling (CuAAC). PGA was derived in aqueous media as well as in organic media using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl morpholinium chloride (DMTTM) salts. The spectra of attached chemical moieties ranges from simple PEGylation with 2,5,8,11,14,17,20-heptaoxadocosan-22-amine (mEG(6)NH2) to the incorporation of propargylamine, 11-azido-3,6,9-trioxaundecan-1-amine (NH2-EG(2)N-3), and 20-azido-3,6,9,12,15,18-hexaoxaicosan-1-amine (NH2-EG(6)N-3). Here…

Click modification of multifunctional liposomes bearing hyperbranched polyether chains.

2014

Aiming at controlled modification of liposomal surface structures, we describe a postpreparational approach for surface derivatization of a new type of multifunctional, sterically stabilized liposomes. Application of dual centrifugation (DC) resulted in high encapsulation efficiencies above 50% at very small batch sizes with a total volume of 150 μL, which were conductive to fast and efficient optimization of variegated surface modification reactions. Cholesterol-polymer amphiphiles, including complex hyperbranched polyether structures bearing 1-4 terminal alkynes, were used in DC formulations to provide steric stabilization. The alkyne moieties were explored as anchors for the conjugation …

2018

The design of multifunctional polymer-based vectors, forming pDNA vaccines, offers great potential in cancer immune therapy. The transfection of dendritic immune cells (DCs) with tumour antigen-encoding pDNA leads to an activation of the immune system to combat tumour cells. In this work, we investigated the chemical attachment of DEC205 antibodies (aDEC205) as DC-targeting structures to polyplexes of P(Lys)-b-P(HPMA). The conjugation of a synthetic block copolymer and a biomacromolecule with various functionalities (aDEC205) requires bioorthogonal techniques to avoid side reactions. Click chemistry and in particular the strain-promoted alkyne-azide cycloaddition (SPAAC) can provide the req…

Polyvinylpolypyrrolidone‐Stabilized Copper Nanoparticles as an Efficient and Recyclable Heterogeneous Catalyst for the Click of 1,2,3‐Triazoles in Wa…

2019

Surface Modification of Nanoparticles and Nanovesicles via Click-Chemistry

2019

Surface modification of nanocarriers offers the possibility of targeted drug delivery, which is of major interest in modern pharmaceutical science. Click-chemistry affords an easy and fast way to modify the surface with targeting structures under mild reaction conditions. Here we describe our current method for the post-preparational surface modification of multifunctional sterically stabilized (stealth) liposomes via copper-catalyzed azide-alkyne cycloaddition (CuAAC) and inverse electron demand Diels-Alder norbornene-tetrazine cycloaddition (IEDDA). We emphasize the use of these in a one-pot orthogonal reaction for deep investigation on stability and targeting of nanocarriers. As the prod…

High-Generation Amphiphilic Janus-Dendrimers as Stabilizing Agents for Drug Suspensions

2018

Pharmaceutical nanosuspensions are formed when drug crystals are suspended in aqueous media in the presence of stabilizers. This technology offers a convenient way to enhance the dissolution of poorly water-soluble drug compounds. The stabilizers exert their action through electrostatic or steric interactions, however, the molecular requirements of stabilizing agents have not been studied extensively. Here, four structurally related amphiphilic Janus-dendrimers were synthesized and screened to determine the roles of different macromolecular domains on the stabilization of drug crystals. Physical interaction and nanomilling experiments have substantiated that Janus-dendrimers with fourth gen…

Copper(II)-dipicolinate-mediated clickable azide–alkyne cycloaddition in water as solvent

2018

Copper(II)-dipicolinate complex [CuIIL(H2O)2] (1) (H2L = dipicolinic acid (H2dipic)) was synthesized via oxidation of copper(I) iodide and pyridine-2,6-dicarboxylic acid in water and acetonitrile in the presence of glycine. Complex 1 was characterized by FT-IR and elemental analysis and its structure confirmed by single crystal X-ray analysis. This complex is an efficient precatalyst that mediates azide-alkyne cycloaddition reactions in water at room temperature either in the absence or presence of a reducing agent. Compound 1-mediated azide-alkyne cycloaddition affords alkyl/aryl substituted 1,2,3-triazole heterocycles in a regioselective manner and excellent yields under very mild reactio…

Expanding the chemical scope of RNA:methyltransferases to site-specific alkynylation of RNA for click labeling.

2010

This work identifies the combination of enzymatic transfer and click labeling as an efficient method for the site-specific tagging of RNA molecules for biophysical studies. A double-activated analog of the ubiquitous co-substrate S-adenosyl-l-methionine was employed to enzymatically transfer a five carbon chain containing a terminal alkynyl moiety onto RNA. The tRNA:methyltransferase Trm1 transferred the extended alkynyl moiety to its natural target, the N2 of guanosine 26 in tRNA(Phe). LC/MS and LC/MS/MS techniques were used to detect and characterize the modified nucleoside as well as its cycloaddition product with a fluorescent azide. The latter resulted from a labeling reaction via Cu(I…