Synthetic ion channels in biomembranes.

Ion transport across cell membranes is crucial in maintaining ion homeostasis in cells. Synthetic molecules that can mimic the functions of natural ion channel proteins would possess great potential as therapeutic agents by promoting apoptosis or interfering with autophagic processes through perturbing the intracellular pH or inducing oxidative and osmotic stresses. However, little is known about the underlying mechanisms in terms of direct correlation between ion transport and biological functions.

Fluoro-Crown Ether Phosphate as Efficient Cell-Permeable Drug Carrier by Disrupting Hydration Layer.

Fast and direct permeation of drug molecules is crucial for effective biotherapeutics. Inspired by a recent finding that fluorous compounds disrupt the hydrogen-bonded network of water, we developed fluoro-crown ether phosphate FP-X. This compound acts as a fast cell-permeating agent, enabling direct delivery of various bioactive cargos (X) into cancer cells without endocytic entrapment.

Monitoring insulin fibrillation kinetics using chromatographic analysis.

Insulin is a small protein widely used to treat patients with diabetes and is a commonly used model for protein fibrillation studies. Under specific conditions, such as low pH and high temperature, insulin monomers aggregate to form fibrils. This aggregation is problematic for manufacturing and storage of insulin.

Fluorocarbon-DNA Conjugates for Enhanced Cellular Delivery: Formation of a Densely Packed DNA Nano-Assembly.

Forming nano-assemblies is essential for delivering DNA conjugates into cells, with the DNA density in the nano-assembly playing an important role in determining the uptake efficiency. In this study, we developed a strategy for the facile synthesis of DNA strands bearing perfluoroalkyl (R) groups (R-DNA conjugates) and investigated how they affect cellular uptake. An R-DNA conjugate bearing a long R group at the DNA terminus forms a nano-assembly with a high DNA density, which results in greatly enhanced cellular uptake.

Synthesis of Short Peptides with Perfluoroalkyl Side Chains and Evaluation of Their Cellular Uptake Efficiency.

With an increasing demand for macromolecular biotherapeutics, the issue of their poor cell-penetrating abilities requires viable and relevant solutions. Herein, we report tripeptides bearing an amino acid with a perfluoroalkyl (R ) group adjacent to the α-carbon. R -containing tripeptides were synthesized and evaluated for their ability to transport a conjugated hydrophilic dye (Alexa Fluor 647) into the cells.

Reconstitution of microtubule into GTP-responsive nanocapsules.

Nanocapsules that collapse in response to guanosine triphosphate (GTP) have the potential as drug carriers for efficiently curing diseases caused by cancer and RNA viruses because GTP is present at high levels in such diseased cells and tissues. However, known GTP-responsive carriers also respond to adenosine triphosphate (ATP), which is abundant in normal cells as well. Here, we report the elaborate reconstitution of microtubule into a nanocapsule that selectively responds to GTP.

Photoreactive Molecular Glue for Enhancing the Efficacy of DNA Aptamers by Temporary-to-Permanent Conjugation with Target Proteins.

We developed a photoreactive molecular glue, Glue-N, which can provide a universal strategy to enhance the efficacy of DNA aptamers by temporary-to-permanent stepwise stabilization of their conjugates with target proteins. As a proof-of-concept study, we applied Glue-N to the SL1 (DNA aptamer)/c-Met (target protein) conjugate system. Glue-N can adhere to and temporarily stabilize this aptamer/protein conjugate multivalently using its guanidinium ion (Gu) pendants that form a salt bridge with oxyanionic moieties (e.

Transferrin-Appended Nanocaplet for Transcellular siRNA Delivery into Deep Tissues.

Transferrin (Tf) is known to induce transcytosis, which is a consecutive endocytosis/exocytosis event. We developed a Tf-appended nanocaplet (NC⊃siRNA) for the purpose of realizing siRNA delivery into deep tissues and RNA interference (RNAi) subsequently. For obtaining NC⊃siRNA, a macromonomer (Gu) bearing multiple guanidinium (Gu) ion units, azide (N) groups, and trityl (Trt)-protected thiol groups in the main chain, side chains, and termini, respectively, was newly designed.