AI Article Synopsis
- The study aimed to investigate how well (123)I-mouse IgG linked to HIV-1 tat protein peptides can enter cells and their nuclei.
- Methods involved modifying mIgG and comparing its internalization and nuclear uptake in various breast cancer cell lines alongside assessing its targeting ability in mice with tumors.
- Results showed a significant nuclear uptake of (123)I-tat-mIgG in cancer cells and highlighted its potential as a basis for developing new radiopharmaceuticals that target intracellular functions.
Article Abstract
Purpose: Our objective was to study the cellular and nuclear uptake of (123)I-mouse IgG ((123)I-mIgG) linked to peptides [GRKKRRQRRRPPQGYGC] harbouring the membrane-translocating and nuclear import sequences of HIV-1 tat protein.
Methods: Carbohydrates on mIgG were oxidized by NaIO(4), then reacted with a 40-fold excess of peptides. Displacement of binding of anti-mouse IgG (Fab specific; alpha-mFab) to (123)I-mIgG by tat-mIgG or mIgG was compared. Internalization and nuclear translocation of (123)I-tat-mIgG in MDA-MB-468, MDA-MB-231 or MCF-7 breast cancer cells were measured. The immunoreactivity of imported tat-mIgG was evaluated by measuring binding of (123)I-alpha-mFab to cell lysate and by displacement of binding of (123)I-mIgG to alpha-mFab by cell lysate. Biodistribution and nuclear uptake of (123)I-tat-mIgG, (123)I-mIgG and (123)I-tat were compared in mice bearing s.c. MDA-MB-468 tumours.
Results: There was a 15-fold decrease in affinity of alpha-mFab for tat-mIgG compared with mIgG. Internalized radioactivity imported into the nucleus for (123)I-tat-mIgG in MDA-MB-468, MDA-MB-231 and MCF-7 cells was 61.5+/-0.6%, 60.3+/-3.6% and 64.7+/-1.0%, respectively. The binding of (123)I-alpha-mFab to lysate from MDA-MB-468 cells importing tat-mIgG was 17-fold higher than that for cells not exposed to tat-mIgG. Imported tat-mIgG competed with tat-mIgG for displacement of binding of (123)I-mIgG to alpha-mFab. Conjugation of mIgG to tat peptides did not change tissue distribution. Nuclear localization for (123)I-tat-mIgG in MDA-MB-468 tumours was 28.1+/-5.6%, and for liver, spleen and kidneys it was 41.7+/-2.7%, 13.8+/-0.8% and 36.9+/-3.3%, respectively.
Conclusion: (123)I-tat-mIgG radioimunoconjugates suggest a route to the design of radiopharmaceuticals exploiting intracellular and nuclear epitopes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00259-005-1908-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A major challenge in epigenetics is uncovering the dynamic distribution of nucleosomes and other DNA-binding proteins, which plays a crucial role in regulating cellular functions. Established approaches such as ATAC-seq, ChIP-seq, and CUT&RUN provide valuable insights but are limited by the ensemble nature of their data, masking the cellular and molecular heterogeneity that is often functionally significant. Recently, long-read sequencing technologies, particularly Single Molecule, Real-Time (SMRT/PacBio) sequencing, have introduced transformative capabilities, such as N6-methyladenine (6mA) footprinting.
View Article and Find Full Text PDFSubmicromolar fluorescence 'turn-on' detection of fluoride anions using -(tetra-aryl) calix[4]pyrrole.
Org Biomol Chem
December 2024
Kangwon National University, Chun Cheon 24341, Korea.
-(tetra-aryl) picket calix[4]pyrrole 1 featuring -fluorophenyl groups at all four -positions in a -configuration has been synthesized and characterized unambiguously using single-crystal X-ray diffraction analysis. This pre-organized system possesses a deep binding pocket created by the four aryl groups so that anions can be accommodated through anion-π interactions and four-point N-H⋯anion hydrogen bonds. Single-crystal X-ray diffraction analysis of the CsF and TEAF (TEA = tetraethylammonium) complexes of receptor 1 unequivocally confirms the formation of 1 : 1 complexes, revealing the binding modes in the solid state.
View Article and Find Full Text PDFDesign of Chemoresponsive Liquid Crystals Using Metal-Coordinating Polymer Surfaces.
ACS Appl Mater Interfaces
December 2024
Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853, United States.
Liquid crystals (LCs), when interfaced with chemically functionalized surfaces, can amplify a range of chemical and physical transformations into optical outputs. While metal cation-binding sites on surfaces have been shown to provide a basis for the design of chemoresponsive LCs, the cations have been found to dissociate from the surfaces and dissolve slowly into LCs, resulting in time-dependent changes in the properties of LC-solid interfaces (which impacts the reliability of devices incorporating such surfaces). Here, we explore the use of surfaces comprising metal-coordinating polymers to minimize the dissolution of metal cations into LCs and characterize the impact of the interfacial environment created by the coordinating polymer on the ordering and time-dependent properties of LCs.
View Article and Find Full Text PDFIsoliquiritigenin Exhibits Anti-Inflammatory Responses in Acute Lung Injury by Covalently Binding to the Myeloid Differentiation Protein-2 Domain.
Phytother Res
December 2024
Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan and Education Ministry of P.R. China, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan Province, China.
Acute lung injury (ALI), a systemic inflammatory response with high morbidity, lacks effective pharmacological therapies. Myeloid differentiation protein-2 (MD2) has emerged as a promising therapeutic target for ALI. Herein, we aimed to evaluate the ability of isoliquiritigenin (ISL), a natural flavonoid found in licorice as a novel MD2 inhibitor, to inhibit lipopolysaccharide (LPS)-induced ALI.
View Article and Find Full Text PDFConformational dynamics of a nicotinic receptor neurotransmitter site.
Elife
December 2024
Computational Biophysics and CADD Group, Computational and Mathematical Biology Center, Translational Health Science and Technology Institute, Faridabad, India.
Agonists enhance receptor activity by providing net-favorable binding energy to active over resting conformations, with efficiency (η) linking binding energy to gating. Previously, we showed that in nicotinic receptors, η-values are grouped into five structural pairs, correlating efficacy and affinity within each class, uniting binding with allosteric activation (Indurthi and Auerbach, 2023). Here, we use molecular dynamics (MD) simulations to investigate the low-to-high affinity transition (L→H) at the Torpedo α-δ nicotinic acetylcholine receptor neurotransmitter site.
View Article and Find Full Text PDFWant 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!