Identification of peptide-based hepatitis B virus capsid inhibitors based on the viral core protein.

In this study, we have identified two novel peptides, 19Ac (comprising residues 91-105) and 20Ac (encompassing residues 96-110), from a systematically designed peptide library based on the Hepatitis B virus (HBV) core protein, that inhibit the assembly of HBV capsid. Peptide 20Ac exhibited about twofold the inhibitory potency of 19Ac and proved effective against both standard and morphothiadin (GLS4)-resistant HBV strains. Molecular dynamics simulations revealed that despite their overlapping sequence, 19Ac and 20Ac bonded to different regions of the core protein, thereby inhibiting capsid assembly through distinct mechanisms.

Late-Stage Derivatization of Oleanolic Acid-Based Anti-HIV-1 Compounds.

A 12-keto-type oleanolic acid derivative (4) has been identified as a potent anti-human immunodeficiency virus type-1 (HIV-1) compound that demonstrates synergistic effects with several types of HIV-1 neutralizing antibodies. In the present study, we used a common key synthetic intermediate to carry out the late-stage derivatization of an anti-HIV compound based on the chemical structure of a 12-keto-type oleanolic acid derivative. To execute this strategy, we designed a diketo-type oleanolic acid derivative (5) for chemoselective transformation, targeting the carboxy group and the hydroxyl group on the statine unit, as well as the 3-carbonyl group on the oleanolic acid unit, as orthogonal synthetic handles.

Amide-to-chloroalkene substitution for overcoming intramolecular acyl transfer challenges in hexapeptidic neuromedin U receptor 2 agonists.

CPN-116 is a peptidic agonist that activates human neuromedin U receptor type 2 (NMUR2) but suffers from chemical instability due to inherent backbone isomerization on the Dap residue. To address this, a Leu-Dap-type ()-chloroalkene dipeptide isostere was synthesized diastereoselectively as a surrogate of the Leu-Dap peptide bond to develop a ()-chloroalkene analogue of CPN-116. The synthesized CPN-116 analogue is stable in 1.

Design, synthesis, and bio-evaluation of novel triterpenoid derivatives as anti-HIV-1 compounds.

Two betulinic acid derivatives, RPR103611 (2) and IC9564 (3) were previously reported to be potent HIV-1 entry inhibitors. In this current study, a SAR study of the triterpenoid moiety of 2 and 3 has been performed and an oleanolic acid derivative (4) was identified as a novel HIV-1 entry inhibitor. In addition, the combination of 4 with several-type of HIV-1 neutralizing antibodies provided significant synergistic effects.

Synthesis and Structural Characterization of β-Turn Mimics Containing ()-Chloroalkene Dipeptide Isosteres.

Described here is the synthetic, spectroscopic, crystallographic, and computational analysis of a series of peptidomimetics containing l-Xaa-d-Yaa-type ()-chloroalkene dipeptide isosteres (CADIs) that were measured in an investigation of the β-turn mimicry of this peptide bond surrogate. We found that the 1,3-allylic strain across the chloroalkene moiety engenders the hyperconjugative interactions between the chloroalkene moiety and the C-H bonding or antibonding orbitals of the C-H bonds in allylic positions. These effects contribute significantly to the stabilization of β-turn structures.

Stereoselective synthesis of highly functionalized ()-chloroalkene dipeptide isosteres containing an α,α-disubstituted amino acid.

Described here is the first stereoselective synthesis of highly functionalized chloroalkene dipeptide isosteres containing an α,α-disubstituted amino acid (ααAA). This synthesis requires the construction of a quaternary carbon center, and this challenge was overcome by the Aza-Darzens condensation of ketimine with α,α-dichloroenolate, producing 2-chloroaziridines with quaternary carbon centers including spirocyclic motifs, which are valuable for the previously elusive synthesis of various ααAA-containing chloroalkene isosteres.

The influence of the combination of visiting frequency of family caregivers and pre-admission frailty status on dependency after discharge among hospitalized older patients: a clinically-based prospective study.

Purpose: This study aims to determine whether the combination of visiting frequency of the family caregiver and frailty status has an additive effect on the incidence of dependency among hospitalized older patients.

Methods: We analyzed the prospective cohort data of hospitalized older patients (65 years and older) with internal medical problems. The main outcome showed patients' dependency from admission to a month after discharge.

Supramolecular Light-Harvesting Antennas of Metal-Coordinated Bis(8-Hydroxyquinoline)-Substituted Porphyrin Networks.

Artificial antenna complexes of metal-coordinated bis(8-hydroxyquinoline)-substituted porphyrin networks that mimic antenna chromophores in plants were organized on titanium dioxide electrodes in photoelectrochemical cells. The generated photocurrents can be optimized according to the two ways of porphyrin self-assembly due to the "antenna effect": changing the number of assembled porphyrin monolayers and the number of generations of the metal-coordinated porphyrin networks.

Preadmission frailty status as a powerful predictor of dependency after discharge among hospitalized older patients: A clinical-based prospective study.

Aim: Frailty is a predictor of several adverse health outcomes in older adults. However, the relationship between preadmission frailty status and the incidence of dependency after discharge in hospitalized older patients remains unclear. The aim of the present study was to determine whether preadmission frailty status can predict dependency after discharge among hospitalized older patients.

Differential Characteristics of Skeletal Muscle in Community-Dwelling Older Adults.

Background: Sarcopenia is diagnosed on the basis of skeletal muscle mass and muscle strength/function. However, more simple and accurate measures for muscle mass and muscle strength/function should be explored.

Objective: The aim of this study was to compare the skeletal muscle characteristics at each stage of sarcopenia (normal, presarcopenia, dynapenia, and sarcopenia) via ultrasonography, multifrequency bioelectrical impedance analysis (BIA), and physical assessment batteries in community-dwelling older adults.

A case grafted with polyglycolic acid sheets and fibrin glue for protection after temporary resection of a metastatic cervical skin tumor.

The aim of this case report was to evaluate the usefulness of a grafting with polyglycolic acid sheet and a fibrin glue spray (PGA sheet grafting) after resection of a cervical skin tumor. A 61-year-old woman presented with left cervical skin tumor resistance to chemo-radiotherapy. She had been undergoing multimodal therapy for ovarian serous papillary adenocarcinoma for the previous six years.