Construction of Nanotube-Shaped mRNA Vehicles Using Self-Assembling Peptides.

The mRNA delivery vehicle technology is one of the key factors in developing mRNA-based therapeutics and vaccines. The delivery vehicle must protect the mRNA from degradation, accurately deliver it across body barriers into the target tissue or cell, and properly regulate expression of the protein. Even though the stability and performance of mRNA delivery vehicles is highly dependent on their nanostructure, most vehicles were irregular spherical shapes.

Stigmurin encapsulated PLA-PEG ameliorates its therapeutic potential, antimicrobial and antiproliferative activities.

In light of growing global challenge posed by antimicrobial resistance, it is very important to explore alternatives that can target pathogenic microorganisms. One such strategy involves the use of antimicrobial peptides (AMPs) and Stigmurin is one such AMP present in Brazilian scorpion Tityus stigmurus which possesses antimicrobial, antiproliferative and antiparasitic activity. The study commenced with successful synthesis and characterization of Stigmurin and its analogues, designated S1 and S2.

Antioxidant Peptide-Based Nanocarriers for Delivering Wound Healing Agents.

Background: Curcumin, a well-known wound healing agent, faces clinical limitations due to its poor water solubility, rapid degradation, and short plasma half-life. To address these challenges, we developed a self-assembling peptide incorporating an antioxidant sequence (YGDEY), which is capable of not only delivering curcumin but also exhibiting additional bioactivity to enhance wound healing.

Methods: An antioxidant nanocarrier was developed via peptide self-assembly.

Theranostics: aptamer-assisted carbon nanotubes as MRI contrast and photothermal agent for breast cancer therapy.

Breast cancer is one of the leading causes of death among women globally, making its diagnosis and treatment challenging. The use of nanotechnology for cancer diagnosis and treatment is an emerging area of research. To address this issue, multiwalled carbon nanotubes (MWCNTs) were ligand exchanged with butyric acid (BA) to gain hydrophilic character.

Adaptable Self-Assembly of a PEG Dendrimer-Coiled Coil Conjugate.

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.

Inhibition of protein-protein interactions using biodegradable depsipeptide nanoassemblies.

Although peptides notoriously have poor intrinsic pharmacokinetic properties, it is well-known that nanostructures with excellent pharmacokinetic properties can be designed. Noticing that peptide inhibitors are generally nonpolar, here, we consolidate the peptide inhibitor targeting intracellular protein-protein interactions (PPIs) as an integral part of biodegradable self-assembled depsipeptide nanostructures (SdPNs). Because the peptide inhibitor has the dual role of PPI inhibition and self-assembly in this design, problems associated with the poor pharmacokinetics of peptides and encapsulation/entrapment processes can be overcome.

Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer.

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.

Magnetic control of self-assembly and disassembly in organic materials.

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).

Pseudo-Isolated α-Helix Platform for the Recognition of Deep and Narrow Targets.

Although interest in stabilized α-helical peptides as next-generation therapeutics for modulating biomolecular interfaces is increasing, peptides have limited functionality and stability due to their small size. In comparison, α-helical ligands based on proteins can make steric clash with targets due to their large size. Here, we report the design of a monomeric pseudo-isolated α-helix (mPIH) system in which proteins behave as if they are peptides.

In pursuit of next-generation therapeutics: Antimicrobial peptides against superbugs, their sources, mechanism of action, nanotechnology-based delivery, and clinical applications.

Antimicrobial peptides (AMPs) attracted attention as potential source of novel antimicrobials. Multi-drug resistant (MDR) infections have emerged as a global threat to public health in recent years. Furthermore, due to rapid emergence of new diseases, there is pressing need for development of efficient antimicrobials.

Unique behaviour of the α-helix in bending deformation.

The maximum degree of bending that can be tolerated by the rigid rod-like α-helix remains unknown; however, it should be very difficult or even impossible to make α-helices with varying degrees of curvature in folded proteins. As an experimentally tractable model, here we utilize cyclic proteins and peptides to determine the maximum possible bending in the α-helix. We artificially enforced bending in the α-helices by using variously sized macrocycles and compared the structural characteristics of the macrocycles with those of their linear counterparts.

Age and Gender Effects on Genotoxicity in Diesel Exhaust Particles Exposed C57BL/6 Mice.

There is growing evidence that the accumulation of DNA damage induced by fine particulate matter (PM) exposure is an underlying mechanism of pulmonary disease onset and progression. However, there is a lack of experimental evidence on whether common factors (age, gender) affect PM induced genomic damage. Here, we assessed the DNA damage potency of PM using conventional genotoxicity testing in old male and female mice aged 8 and 40 weeks.

Disaggregation of Amyloid-β Plaques by a Local Electric Field Generated by a Vertical Nanowire Electrode Array.

The aggregation and accumulation of amyloid-β (Aβ) peptides is a characteristic pathology for Alzheimer's disease (AD). Although noninvasive therapies involving stimulation by electric field (EF) have been reported, the efficiency of Aβ disaggregation needs to be further improved for this strategy to be used in clinical settings. In this study, we show that an electrode based on a vertical nanowire electrode array (VNEA) is far more superior to a typical flat-type electrode in disaggregating Aβ plaques.

A Dodecapeptide Selected by Phage Display as a Potential Theranostic Probe for Colon Cancers.

Aim: Colon cancer is one of the leading causes of cancer-related mortality. However, specific biomarkers for its diagnosis or treatment are not established well.

Methods: We developed a colon-cancer specific peptide probe using phage display libraries.

Self-Assembling Peptides and Their Application in the Treatment of Diseases.

Self-assembling peptides are biomedical materials with unique structures that are formed in response to various environmental conditions. Governed by their physicochemical characteristics, the peptides can form a variety of structures with greater reactivity than conventional non-biological materials. The structural divergence of self-assembling peptides allows for various functional possibilities; when assembled, they can be used as scaffolds for cell and tissue regeneration, and vehicles for drug delivery, conferring controlled release, stability, and targeting, and avoiding side effects of drugs.

Synthesis and purification of self-assembling peptide-oligonucleotide conjugates by solid-phase peptide fragment condensation.

Peptide-oligonucleotide conjugates (POCs) are interesting molecules as they covalently combine 2 of the most important biomacromolecules. Sometimes, the synthesis of POCs involves unexpected difficulties; however, POCs with self-assembling propensity are even harder to synthesize and purify. Here, we show that solid-phase peptide fragment condensation combined with thiol-maleimide or copper-catalyzed azide-alkyne cycloaddition click chemistries is useful for the syntheses of self-assembling POCs.