You Jin Jung

All Publications

• Cooperative Assembly of Self-Adjusting a-Helical Coiled Coils along the Length of an mRNA Chain to Form a Thermodynamically Stable Nanotube Carrier JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Jung, Y., Choi, J., Ryu, J., Zhang, Z., Lim, Y. 2023; 145 (42): 23048-23056

  Abstract

  Although mRNA delivery technology is very promising, problems in safety and transport arise due to the intrinsically low thermodynamic stability of the current mRNA carriers. Considering that mRNAs are filamentous and a nanotube is one of the most thermodynamically stable shapes among nanoassemblies, a nanotube is one of the most stable supramolecular structures that can be assembled with mRNA. Here, we develop a nanotube-shaped filamentous mRNA delivery platform that shows exceptionally high thermodynamic stability. The key to the development of the mRNA nanotube is the design of self-adjusting supramolecular building blocks (SABs) that have two disparate properties, i.e., dynamic property and stiffness, in a single molecule. The counterbalance of the dynamic property and stiffness in SABs enables the coating of mRNA by winding its way through the flexible and irregular mRNA chain via cooperative interactions. SAB nanotubes with targeting ligands installed show a high uptake efficiency in mammalian cells and controllable gene expression behavior. Thus, the mRNA nanotube provides an enabling technology toward the development of safe and stable mRNA vaccines and therapeutics.

  View details for DOI 10.1021/jacs.3c05638

  View details for Web of Science ID 001071406200001

  View details for PubMedID 37735109

• Magnetic control of self-assembly and disassembly in organic materials NATURE COMMUNICATIONS Jung, Y., Kim, H., Cheong, H., Lim, Y. 2023; 14 (1): 3081

  Abstract

  Because organic molecules and materials are generally insensitive or weakly sensitive to magnetic fields, a certain means to enhance their magnetic responsiveness needs to be exploited. Here we show a strategy to amplify the magnetic responsiveness of self-assembled peptide nanostructures by synergistically combining the concepts of perfect α-helix and rod-coil supramolecular building blocks. Firstly, we develop a monomeric, nonpolar, and perfect α-helix (MNP-helix). Then, we employ the MNP-helix as the rod block of rod-coil amphiphiles (rod-coils) because rod-coils are well-suited for fabricating responsive assemblies. We show that the self-assembly processes of the designed rod-coils and disassembly of rod-coil/DNA complexes can be controlled in a magnetically responsive manner using the relatively weak magnetic field provided by the ordinary neodymium magnet [0.07 ~ 0.25 Tesla (T)]. These results demonstrate that magnetically responsive organic assemblies usable under practical conditions can be realized by using rod-coil supramolecular building blocks containing constructively organized diamagnetic moieties.

  View details for DOI 10.1038/s41467-023-38846-2

  View details for Web of Science ID 001029731000021

  View details for PubMedID 37248227

  View details for PubMedCentralID PMC10227084

• Adaptable Self-Assembly of a PEG Dendrimer-Coiled Coil Conjugate CHEMPLUSCHEM Lee, Y., Jung, Y., Lim, Y. 2024; 89 (9): e202400114

  Abstract

  Self-assembly of designed molecules has enabled the construction of a variety of functional nanostructures. Specifically, adaptable self-assembly has demonstrated several advantageous features for smart materials. Here, we demonstrate that an α-helical coiled coil conjugated with a dendrimer can adapt to spatial restriction due to the strong steric repulsion between dendrimer chains. The adaptable transformation of a tetrameric coiled coil to a trimeric coiled coil can be confirmed using analytical ultracentrifugation upon conjugation of the dendrimer to the coiled coil-forming building block. Interestingly, circular dichroism spectroscopy analysis of the dendrimer conjugate revealed an unconventional trend: the multimerization of the coiled coil is inversely dependent on concentration. This result implies that the spatial crowding between the bulky dendritic chains is significantly stronger than that between linear chains, thereby affecting the overall assembly process. We further illustrated the application potential by decorating the surface of gold nanorods (AuNRs) with the adaptable coiled coil. The dendrimer-coiled coil peptide conjugate can be utilized to fabricate organic-inorganic nanohybrids with enhanced colloidal and thermal stabilities. This study demonstrates that the coiled coil can engage in the adaptable mode of self-assembly with the potential to form dynamic peptide-based materials.

  View details for DOI 10.1002/cplu.202400114

  View details for Web of Science ID 001262351200001

  View details for PubMedID 38797707

• Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer CHEMICAL SCIENCE Ko, S., Kim, J., Park, J., Jung, Y., Choi, M., Jin, K., Kim, Y., Lim, Y., Jeong, W. 2023; 14 (35): 9600-9607

  Abstract

  This study presents the development of a β-hairpin (tryptophan zipper, Trpzip)-based molecular tweezer (MT) that can control the folding and binding of α-helical peptides. When an α-helix isolated from the p53 protein was conjugated with Trpzip in an optimized macrocyclic structure, the folded β-hairpin stabilized the helix conformation through the side chain-to-side chain stapling strategy, which notably enhanced target (hDM2) affinity of the peptide. On the other hand, the helicity and binding affinity were significantly reduced when the hairpin was unfolded by a redox stimulus. This stimulus-responsive property was translated into the effective capture and release of model multivalent biomaterials, hDM2-gold nanoparticle conjugates. Since numerous protein interactions are mediated by α-helical peptides, these results suggest that the β-hairpin-based MT holds great potential to be utilized in various biomedical applications, such as protein interaction inhibition and cancer biomarker (e.g., circulating tumor cells and exosomes) detection.

  View details for DOI 10.1039/d3sc03758d

  View details for Web of Science ID 001055773600001

  View details for PubMedID 37712040

  View details for PubMedCentralID PMC10498507

• Structural control of self-assembled peptide nanostructures to develop peptide vesicles for photodynamic therapy of cancer MATERIALS TODAY BIO Kwon, S., Lee, D., Kim, H., Jung, Y., Koo, H., Lim, Y. 2022; 16: 100337

  Abstract

  Vesicles such as liposomes, polymersomes, and exosomes have been widely used as drug delivery carriers; however, peptide vesicles (peptidesomes) despite their potential utility are far less well developed. Peptidesomes are distinctive because peptides play dual roles as a self-assembly building block and a bioactive functional unit. In order for peptidesomes to become successful nanodrugs, the issues related to differences in nanostructural properties between in vitro and in vivo conditions should be addressed. Here, we delineate a multivariate approach to feedback control the structures of peptide building blocks, nanoparticle size, drug loading process, nanoparticle aggregation, cytotoxicity, cell targeting capability, endosome disruption function, protease resistance, and in vivo performance, which eventually enabled the successful development of a highly efficacious peptidesome for in vivo cancer therapy. This study lays the groundwork for the successful in vivo translation of peptide nanodrugs.

  View details for DOI 10.1016/j.mtbio.2022.100337

  View details for Web of Science ID 000860720000002

  View details for PubMedID 35799895

  View details for PubMedCentralID PMC9254122