Chimeric VLPs
Paul Pumpens in Single-Stranded RNA Phages, 2020
Meanwhile, Hong et al. (2008) improved the CuAAC reaction by the use of an electrochemical potential to maintain catalysts in the active CuI oxidation state in the presence of air. This simple procedure efficiently achieved excellent yields of the CuAAC products without the use of potentially damaging chemical reducing agents. The electrochemically protected bioconjugations in air were performed with the Qβ VLPs that were derivatized with azide moieties at surface lysine residues, and complete derivatization of more than 600 reactive sites per particle was demonstrated (Hong et al. 2008). The optimized CuAAC reaction was reviewed under the headline “How to Click with Biomolecules” as the most widely recognized example of the click chemistry applications (Hong et al. 2009). At the same, Strable and Finn (2009) reviewed the principles of the chemical modification of viruses and virus-like particles. The principles and approach of the CuAAC reaction in connection with the Qβ VLPs, among other substrates, were reviewed further in detail (Lallana et al. 2011, 2012; Such et al. 2012; Levine et al. 2013; Kim H et al. 2015).
Orders Norzivirales and Timlovirales
Paul Pumpens, Peter Pushko, Philippe Le Mercier in Virus-Like Particles, 2022
Meanwhile, Hong V et al. (2008) improved the CuAAC reaction by the use of an electrochemical potential to maintain catalysts in the active CuI oxidation state in the presence of air. This simple procedure efficiently achieved excellent yields of the CuAAC products without the use of potentially damaging chemical reducing agents. The electrochemically protected bioconjugations in air were performed with the Qβ VLPs that were derivatized with azide moieties at surface lysine residues, and complete derivatization of more than 600 reactive sites per particle was demonstrated (Hong V et al. 2008). The optimized CuAAC reaction was reviewed under the headline “How to click with biomolecules” as the most widely recognized example of the click chemistry applications (Hong V et al. 2009). At the same, Strable and Finn (2009) reviewed the principles of the chemical modification of viruses and virus-like particles. The principles and approach of the CuAAC reaction in connection with the Qβ VLPs, among other substrates, were reviewed further in detail (Lallana et al. 2011, 2012; Such et al. 2012; Levine et al. 2013; Kim H et al. 2015).
Nanosuspensions as Nanomedicine: Current Status and Future Prospects
Debarshi Kar Mahapatra, Sanjay Kumar Bharti in Medicinal Chemistry with Pharmaceutical Product Development, 2019
Aggregation may occur either during preparation process or storage. In case of top-down approach for nanosuspension production, as the surface area increases, nano-sized drug particles aggregate due to thermodynamic effects, ultimately reducing the process efficiency [98]. Thus, the use of a stabilizer to cover the surface of nanoparticles during milling or homogenizing is important. During storage, aggregation becomes even more important. The selection of appropriate stabilizers and concentrations are critical parameters of stability [99]. Functional co-polymers bearing alkynyl or azido groups have been reported to prevent aggregation by “click-chemistry”-mediated crosslinking [100]. The successful cross-linking of the polymers around the drug nanosuspensions may prevent aggregation and control the dissolution rate, thus stabilizing the drug nanosuspensions.
In situ gelling and mucoadhesive polymers: why do they need each other?
Published in Expert Opinion on Drug Delivery, 2018
Forouhe Zahir-Jouzdani, Julian Dominik Wolf, Fatemeh Atyabi, Andreas Bernkop-Schnürch
Click chemistry comprises practical and reliable reactions allowing for modular synthesis of larger molecules. ‘Spring loaded’ reactants form carbon-heteroatom bonds via different mechanisms such as strain-promoted azide-alkyne cycloaddition (SPAAC), [3 + 2] cycloaddition or Diels-Alder cycloaddition. Within the last years this approach has aroused more and more interest for the development of in situ gelling systems. For example, azadibenzocyclooctyne and azide functionalized PEG chains were used to generate cross-linked polymer networks via SPAAC. Without need for catalysts or external stimuli these systems gelled within seconds and mechanical as well as rheological properties were adjustable by varying the molecular mass and degree of substitution of the PEG [45]. Truong et al. [11] chose a dual-click approach to achieve a tough double network under physiological conditions. A loose network was generated via tetrazine-norbornene inverse-electron demand Diels-Alder cycloaddition between norbornene-functionalized CS and PEG-ditetrazine, whereas nucleophilic thiol-alkyne addition between PEG-dithiol and PEG-tetraalkyne formed the dense network. In this way, they were able to prepare a hydrogel exhibiting high mechanical strength as well as small pore sizes being suitable for a range of applications.
Nanoparticle-based drug delivery in the inner ear: current challenges, limitations and opportunities
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Rahul Mittal, Stefanie A. Pena, Angela Zhu, Nicolas Eshraghi, Arian Fesharaki, Elijah J. Horesh, Jeenu Mittal, Adrien A. Eshraghi
The surface of NPs can be modified to target specific structures by conjugating ligands to the surface using bio-conjugation techniques. Some newer methods include expressed protein ligation (EPL) and click chemistry [36,37]. In EPL, a site-specific chemical ligation is made between a recombinant protein with a C-terminal thioester and a peptide or protein with an N-terminal cysteine. A C-terminal thioester can then be added onto a targeting ligand through the use of inteins (autoprocessing proteins) which are then placed between the ligand and an affinity tag. After bacterial expression and affinity purification steps, the ligand is released from the affinity tag to create a reactive thioester at the C-terminus. The thioester can then react with any peptide containing an N-terminal cysteine [17]. On the other hand, click chemistry adds ligands to NPs through a Cu I- catalyzed terminal alkyne-azide cycloaddition [17]. A drawback of click chemistry is the reaction process, which may degrade or modify the target of interest. Recently, EPL and click chemistry techniques have been combined to allow for the conjugation of targeting ligands to NPs that are site specific. The combined method allows for a stereospecific ligand attachment onto the NP surface. This method has been used to conjugate full antibodies, peptides and drugs onto the NP surface [38].
Proteomics for cancer drug design
Published in Expert Review of Proteomics, 2019
Amanda Haymond, Justin B. Davis, Virginia Espina
In chemoproteomics, bioactive small molecules, the chemical probes, are screened against cellular extracts or in vitro protein panels to identify high affinity binding partners. The probe and its associated protein are retrieved and proteins are usually identified by mass spectrometry. Affinity-based techniques affix the small molecule to a bead or similar moiety to facilitate extraction of the small molecule and its binding partners [52]. Activity-based techniques require co-incubation of the small molecule with an enzyme, such that it reacts with and covalently bonds to the enzyme’s active site. A linker segment connects the small molecule to a retrieval and/or detection moiety [53]. Click chemistry can be used to conjugate linkers to proteins or other macromolecules for retrieval [54]. This approach allows the original probe to be small and flexible in order to interact with the target enzyme, but facilitates retrieval after the substrate is covalently bound to the enzyme.
Related Knowledge Centers
- Biomolecule
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