Dual-modified penetratin peptides: Enhancing nucleic acid delivery through stapling and endosomal escape domain.

Cell-penetrating peptides (CPPs) are crucial for delivering macromolecules such as nucleic acids into cells. This study investigates the effectiveness of dual-modified penetratin peptides, focusing on the impact of stapling structures and an endosomal escape domain (EED) on enhancing intracellular uptake. Some CPPs were synthesized with an EED at either the N- or C-terminus and stapling structures, and then complexed with plasmid DNA (pDNA) to evaluate their cellular uptake.

Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers.

Cell-penetrating peptides (CPPs) are widely used for the intracellular delivery of a variety of cargo molecules, including small molecules, peptides, nucleic acids, and proteins. Many cationic and amphiphilic CPPs have been developed; however, there have been few reports regarding hydrophobic CPPs. Herein, we have developed stapled hydrophobic CPPs based on the hydrophobic CPP, TP10, by introducing an aliphatic carbon side chain on the hydrophobic face of TP10.

In silico optimization of peptides that inhibit Wnt/β-catenin signaling.

The Wnt/β-catenin signaling pathway causes transcriptional activation through the interaction between β-catenin and T cell-specific transcription factor (TCF) and regulates a wide variety of cellular responses, including proliferation, differentiation and cell motility. Excessive transcriptional activation of the Wnt/β-catenin pathway is implicated in developing or exacerbating various cancers. We have recently reported that liver receptor homolog-1 (LRH-1)-derived peptides inhibit the β-catenin/TCF interaction.

Oligoarginine-Conjugated Peptide Foldamers Inhibiting Vitamin D Receptor-Mediated Transcription.

The vitamin D receptor (VDR) is a nuclear receptor, which is involved in several physiological processes, including differentiation and bone homeostasis. The VDR is a promising target for the development of drugs against cancer and bone-related diseases. To date, several VDR antagonists, which bind to the ligand binding domain of the VDR and compete with the endogenous agonist 1α,25(OH)D, have been reported.

Development of a penetratin-conjugated stapled peptide that inhibits Wnt/β-catenin signaling.

Wnt/β-catenin pathway triggers the formation of a complex between β-catenin and T cell-specific transcription factor (TCF), which induces transcriptional activation. Excessive transcriptional activation of this pathway is associated with the development, cause, and deterioration of various cancers. Therefore, the Wnt/β-catenin pathway is an attractive drug target for cancer therapeutics and small molecule- and peptide-based protein-protein interaction (PPI) inhibitors have been developed.

Helix-Stabilized Cell-Penetrating Peptides for Delivery of Antisense Morpholino Oligomers: Relationships among Helicity, Cellular Uptake, and Antisense Activity.

The secondary structures of cell-penetrating peptides (CPPs) influence their properties including their cell-membrane permeability, tolerability to proteases, and intracellular distribution. Herein, we developed helix-stabilized arginine-rich peptides containing α,α-disubstituted α-amino acids and their conjugates with antisense phosphorodiamidate morpholino oligomers (PMOs), to investigate the relationships among the helicity of the peptides, cellular uptake, and antisense activity of the peptide-conjugated PMOs. We demonstrated that helical CPPs can efficiently deliver the conjugated PMO into cells compared with nonhelical CPPs and that their antisense activities are synergistically enhanced in the presence of an endosomolytic reagent or an endosomal escape domain peptide.

Peptide Stapling Improves the Sustainability of a Peptide-Based Chimeric Molecule That Induces Targeted Protein Degradation.

Peptide-based target protein degradation inducers called PROTACs/SNIPERs have low cell penetrability and poor intracellular stability as drawbacks. These shortcomings can be overcome by easily modifying these peptides by conjugation with cell penetrating peptides and side-chain stapling. In this study, we succeeded in developing the stapled peptide stPERML-R7, which is based on the estrogen receptor alpha (ERα)-binding peptide PERML and composed of natural amino acids.

Design, Synthesis, and Biological Activity of Conformationally Restricted Analogues of Silibinin.

Silibinin (Sib), one of the main components of milk thistle extract, has attracted considerable attention because of its various biological activities, which include antioxidant activity and potential effects in diabetes and Alzheimer's disease (AD). In a previous study, we synthesized catechin analogues by constraining the geometries of (+)-catechin and (-)-epicatechin. The constrained analogues exhibited enhanced bioactivities, with the only major difference between the two being their three-dimensional structures.

Development of Photoswitchable Estrogen Receptor Ligands.

Photopharmacology has attracted attention as an approach for the development of novel therapeutics because it allows regulation of the bioactivity of compounds based on their conformational change by photo-irradiation. Previously, we have reported several types of selective estrogen receptor (ER) modulators based on diphenylmethane skeleton. To develop novel photopharmacological reagents, we designed and synthesized a set of ER ligands based on azobenzene skeleton, which can switch its conformation following UV irradiation.

Basic Gas-Sensing Properties of Photoluminescent Eu₂O₃-Mixed SnO₂-Based Materials with Submicron-Size Macropores.

Macroporous SnO₂ films mixed with 2.5 mol% Eu₂O₃ and mol% MgO (mp-Eu₂O₃/SnO₂(MgO)) were fabricated by a modified sol-gel technique employing polymethylmethacrylate microspheres (ca. 800 nm in diameter) as a template, and their photoluminescence (PL) intensities under various gaseous atmospheric conditions and gas-response behavior were investigated under the UV-light irradiation (wavelength: 260 nm) at a room temperature of ca.

Differential expressions of melanocortin receptor subtypes in melanophores and xanthophores of barfin flounder.

alpha-Melanocyte-stimulating hormone (alpha-MSH) is a member of the melanocortin (MC) family, and the MC receptor (MCR) is a member of the G protein-coupled receptor (GPCR) superfamily. We previously found that in barfin flounder, a flatfish, alpha-MSH with an acetyl group at the N-terminus stimulated pigment dispersion in xanthophores; however, this effect was not observed in melanophores. Therefore, the present study was undertaken to find which MCR subtypes are expressed in these pigment cells in order to elucidate how acetylation regulates activities of alpha-MSH-related peptides.

Food deprivation increases the expression of melanocortin-4 receptor in the liver of barfin flounder, Verasper moseri.

The melanocortin (MC) system is composed of melanocyte-stimulating hormone, adrenocorticotropic hormone and their receptors. The MC system has a role in both pigmentation and the regulation of energy homeostasis, in which MC4R, one of the five MC receptors, has a key role. Interestingly, the barfin flounder (Pleuronectiformes) reared with a black background shows retarded growth compared to white background-reared fish, which could be associated with the MC system because of its dual role in regulating pigmentation and energy status.

Possible involvement of melanin-concentrating hormone in food intake in a teleost fish, barfin flounder.

We investigated the involvement of MCH in food intake in barfin flounder. The structure of barfin flounder MCH was determined by cDNA cloning and mass spectrometry. In fasted fish, the MCH gene expression and the number of MCH neurons in the brain were greater than controls.