199192-20-6Relevant articles and documents
Cyclopropanation of C60 with malonic acid mono-esters
Nierengarten, Jean-Francois,Nicoud, Jean-Francois
, p. 7737 - 7740 (1997)
Reaction of C69 with malonic acid mono-esters in the presence of iodine and diazabicyclo[5.4.0]undec-7-ene (DBU) provides the corresponding 61-iodo- 1,2-methano[60]fullerene-61-carboxylates. This cyclopropanation of C60 seems to occur via a carbenoid intermediate.
Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers
Zhang, Dapeng,Atochina-Vasserman, Elena N.,Maurya, Devendra S.,Liu, Matthew,Xiao, Qi,Lu, Juncheng,Lauri, George,Ona, Nathan,Reagan, Erin K.,Ni, Houping,Weissman, Drew,Percec, Virgil
supporting information, p. 17975 - 17982 (2021/11/10)
Targeted and efficient delivery of nucleic acids with viral and synthetic vectors is the key step of genetic nanomedicine. The four-component lipid nanoparticle synthetic delivery systems consisting of ionizable lipids, phospholipids, cholesterol, and a PEG-conjugated lipid, assembled by microfluidic or T-tube technology, have been extraordinarily successful for delivery of mRNA to provide Covid-19 vaccines. Recently, we reported a one-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimer (IAJD) synthetic delivery system for mRNA relying on amphiphilic Janus dendrimers and glycodendrimers developed in our laboratory. Amphiphilic Janus dendrimers consist of functional hydrophilic dendrons conjugated to hydrophobic dendrons. Co-assembly of IAJDs with mRNA into dendrimersome nanoparticles (DNPs) occurs by simple injection in acetate buffer, rather than by microfluidic devices, and provides a very efficient system for delivery of mRNA to lung. Here we report the replacement of most of the hydrophilic fragment of the dendron from IAJDs, maintaining only its ionizable amine, while changing its interconnecting group to the hydrophobic dendron from amide to ester. The resulting IAJDs demonstrated that protonated ionizable amines play dual roles of hydrophilic fragment and binding ligand for mRNA, changing delivery from lung to spleen and/or liver. Replacing the interconnecting ester with the amide switched the delivery back to lung. Delivery predominantly to liver is favored by pairs of odd and even alkyl groups in the hydrophobic dendron. This simple structural change transformed the targeted delivery of mRNA mediated with IAJDs, from lung to liver and spleen, and expands the utility of DNPs from therapeutics to vaccines.
Rational Design of Supramolecular Dynamic Protein Assemblies by Using a Micelle-Assisted Activity-Based Protein-Labeling Technology
Sandanaraj, Britto S.,Reddy, Mullapudi Mohan,Bhandari, Pavankumar Janardhan,Kumar, Sugam,Aswal, Vinod K.
supporting information, p. 16085 - 16096 (2018/10/15)
The self-assembly of proteins into higher-order superstructures is ubiquitous in biological systems. Genetic methods comprising both computational and rational design strategies are emerging as powerful methods for the design of synthetic protein complexes with high accuracy and fidelity. Although useful, most of the reported protein complexes lack a dynamic behavior, which may limit their potential applications. On the contrary, protein engineering by using chemical strategies offers excellent possibilities for the design of protein complexes with stimuli-responsive functions and adaptive behavior. However, designs based on chemical strategies are not accurate and therefore, yield polydisperse samples that are difficult to characterize. Here, we describe simple design principles for the construction of protein complexes through a supramolecular chemical strategy. A micelle-assisted activity-based protein-labeling technology has been developed to synthesize libraries of facially amphiphilic synthetic proteins, which self-assemble to form protein complexes through hydrophobic interaction. The proposed methodology is amenable for the synthesis of protein complex libraries with molecular weights and dimensions comparable to naturally occurring protein cages. The designed protein complexes display a rich structural diversity, oligomeric states, sizes, and surface charges that can be engineered through the macromolecular design. The broad utility of this method is demonstrated by the design of most sophisticated stimuli-responsive systems that can be programmed to assemble/disassemble in a reversible/irreversible fashion by using the pH or light as trigger.
