Cell-Surface-Retained Peptide Additives for the Cytosolic Delivery of Functional Proteins.

The delivery of functional proteins remains a major challenge in advancing biological and pharmaceutical sciences. Herein, we describe a powerful, simple, and highly effective strategy for the intracellular delivery of functional cargoes. Previously, we demonstrated that cell-penetrating peptide (CPP) additives equipped with electrophilic thiol-reactive moieties temporarily attach to the cellular membrane, thereby facilitating the cellular uptake of protein- and antibody-CPP cargoes through direct membrane transduction at low concentrations.

Targeted Subcellular Protein Delivery Using Cleavable Cyclic Cell-Penetrating Peptide-Conjugates.

Proteins conjugated to cyclic cell-penetrating peptides (cCPPs) haAbstractve been shown to be effectively taken up by living cells. Conjugation of proteins to cCPPs in a cleavable manner leads to localization in the cytosol and immediate bioavailability of the protein after uptake. Here we describe how mCherry, a fluorescent protein, can be targeted to a membrane-bound compartment, the nucleus, and a subcellular structure like the actin cytoskeleton after cCPP-mediated uptake into living cells.

Diethynyl Phosphinates for Cysteine-Selective Protein Labeling and Disulfide Rebridging.

Diethynyl phosphinates were developed as bisfunctional electrophiles for the site-selective modification of peptides, proteins and antibodies. One of their electron-deficient triple bonds reacts selectively with a thiol and positions an electrophilic moiety for a subsequent intra- or intermolecular reaction with another thiol. The obtained conjugates were found to be stable in human plasma and in the presence of small thiols.

De Novo Radiomics Approach Using Image Augmentation and Features From T1 Mapping to Predict Gleason Scores in Prostate Cancer.

Objectives: The aims of this study were to discriminate among prostate cancers (PCa's) with Gleason scores 6, 7, and ≥8 on biparametric magnetic resonance imaging (bpMRI) of the prostate using radiomics and to evaluate the added value of image augmentation and quantitative T1 mapping.

Materials And Methods: Eighty-five patients with subsequently histologically proven PCa underwent bpMRI at 3 T (T2-weighted imaging, diffusion-weighted imaging) with 66 patients undergoing additional T1 mapping at 3 T. The PCa lesions as well as the peripheral and transition zones were segmented pixel by pixel in multiple slices of the 3D MRI data sets (T2-weighted images, apparent diffusion coefficient, and T1 maps).

Sensitization of Human Liver Cells Toward Fas-Mediated Apoptosis by the Metabolically Activated Pyrrolizidine Alkaloid Lasiocarpine.

Scope: Pyrrolizidine alkaloids (PAs) are common phytotoxins. Intoxication can lead to liver damage. Previous studies showed PA-induced apoptosis in liver cells.

Targeted Subcellular Protein Delivery Using Cleavable Cyclic Cell-Penetrating Peptides.

The delivery of entire functional proteins into living cells is a long-sought goal in science. Cyclic cell-penetrating peptides (cCPPs) have proven themselves to be potent delivery vehicles to carry proteins upon conjugation into the cytosol of living cells with immediate bioavailability via a non-endosomal uptake pathway. With this strategy, we pursue the cytosolic delivery of mCherry, a medium-sized fluorescent protein.