Mirror image peptides have unique stability and immunogenic properties in mammals, making them attractive agents to investigate. Their properties inside cells have been mostly unexplored because biopolymers are difficult to transport across cellular membranes. Here, we used protective antigen (PA) from anthrax toxin to deliver mirror image polypeptide cargo into the cytosol of mammalian cells when conjugated to the C-terminus of the PA-binding domain of lethal factor, LF. We found mirror image polypeptides and proteins were translocated as efficiently into cells as their L counterparts. Once in the cytosol, by the use of western blot, we found that d peptides at the C-terminus of LF were able to achieve higher steady state concentrations when compared to the l-peptide conjugate. With this platform, we delivered a d-peptide MDM2 antagonist to disrupt the p53/MDM2 interaction in cancer cells. For the first time, we show the PA/LF system is adaptable for the intracellular delivery of mirror image peptides and proteins.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492103 | PMC |
| http://dx.doi.org/10.1039/c4sc02078b | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Axially Chiral TADF Imidazolium Salts for Circularly Polarized Light-Emitting Electrochemical Cells.
Angew Chem Int Ed Engl
January 2025
Institute of Chemistry Chinese Academy of Sciences, CAS Key Laboratory of Molecular Recognition and Function, CHINA.
A pair of axially chiral thermally activated delayed fluorescent (TADF) enantiomers, R-TCBN-ImEtPF6 and S-TCBN-ImEtPF6, with intrinsic ionic characteristics were efficiently synthesized by introducing imidazolium hexafluorophosphate to chiral TADF unit. The TADF imidazolium salts exhibited a high photoluminescence quantum yield (PLQY) of up to 92%, a small singlet-triplet energy gap (∆EST) of 0.04 eV, as well as reversible redox properties.
View Article and Find Full Text PDFTemporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is associated with a complex genetic architecture, but the translation from genetic risk factors to brain vulnerability remains unclear. Here, we examined associations between epilepsy-related polygenic risk scores for HS (PRS-HS) and brain structure in a large sample of neurotypical children, and correlated these signatures with case-control findings in in multicentric cohorts of patients with TLE-HS. Imaging-genetic analyses revealed PRS-related cortical thinning in temporo-parietal and fronto-central regions, strongly anchored to distinct functional and structural network epicentres.
View Article and Find Full Text PDFA mirror-image experiment: Sorting carbon nanotubes by L-DNA.
PNAS Nexus
January 2025
Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003, USA.
DNA has found increasing applications in molecular engineering, yet its chiral property has rarely been utilized. Here, we report a mirror-image experiment using naturally occurring D-DNA and its enantiomer L-DNA to sort a chiral mixture of single-wall carbon nanotubes (SWCNTs). We find that parity conservation leads to a robust experimental outcome: changing DNA chirality results in handedness inversion of the purified nanotube.
View Article and Find Full Text PDFHippocampal Functional Radiomic Features for Identification of the Cognitively Impaired Patients from Low-Back-Related Pain: A Prospective Machine Learning Study.
J Pain Res
January 2025
Jiangxi Provincial Key Laboratory for Precision Pathology and Intelligent Diagnosis, Department of Radiology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People's Republic of China.
Purpose: To investigate whether functional radiomic features in bilateral hippocampi can identify the cognitively impaired patients from low-back-related leg pain (LBLP).
Patients And Methods: For this retrospective study, a total of 95 clinically definite LBLP patients (40 cognitively impaired patients and 45 cognitively preserved patients) were included, and all patients underwent functional MRI and clinical assessments. After calculating the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), voxel-mirrored homotopic connectivity (VMHC) and degree centrality (DC) imaging, the radiomic features (n = 819) of bilateral hippocampi were extracted from these images, respectively.
Three-dimensional analysis of facial morphology in nine-year-old children with different unilateral orofacial clefts compared to normative data.
PeerJ
January 2025
Section of Orthodontics and Craniofacial Biology, Department of Dentistry, Radboud University Medical Center, Nijmegen, Netherlands.
Aim: To compare three-dimensional (3D) facial morphology of various unilateral cleft subphenotypes at 9-years of age to normative data using a general face template and automatic landmarking. The secondary objective is to compare facial morphology of 9-year-old children with unilateral fusion to differentiation defects.
Methods: 3D facial stereophotogrammetric images of 9-year-old unilateral cleft patients were imported into 3DMedX® for processing.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!