Per- and Polyfluoroalkyl (PFAS) Disruption of Thyroid Hormone Synthesis.

Per- and polyfluoroalkyl substances (PFAS) are a group of environmental pollutants that have been linked to a variety of health problems in humans, including the disruption of thyroid functions. Herein, for the first time, the impact of PFAS on thyroid hormone synthesis is shown. Mid- to long-chain PFAS impact thyroid hormone synthesis by changing the local hydrogen bond network as well as the required orientation of hormonogenic residues, stopping the production of thyroxine (T4).

Interaction of Per- and Polyfluoroalkyl Substances with Estrogen Receptors in Rainbow Trout (): An Investigation.

Fresh water sources, including lakes, such as the Great Lakes, are some of the most important ecosystems in the world. Despite the importance of these lakes, there is increasing concern about the presence of per- and polyfluoroalkyl substances (PFAS)─among the most prevalent contaminants of our time─due to the ability of PFAS to bioaccumulate and persist in the environment, as well as to its linkages to detrimental human and animal health effects. In this study, PFAS exposure on rainbow trout () is examined at the molecular level, focusing on the impact of PFAS binding on the alpha (α) and beta (β) estrogen receptors (ERs) using molecular dynamics simulations, binding free energy calculations, and structural analysis.

Solid-Phase-Supported Chemoenzymatic Synthesis and Analysis of Chondroitin Sulfate Proteoglycan Glycopeptides.

Proteoglycans (PGs), consisting of glycosaminoglycans (GAGs) linked with the core protein through a tetrasaccharide linkage region, play roles in many important biological events. The chemical synthesis of PG glycopeptides is extremely challenging. In this work, the enzymes required for synthesis of chondroitin sulfate (CS) PG (CSPG) have been expressed and the suitable sequence of enzymatic reactions has been established.

Binding of Per- and Polyfluoroalkyl Substances (PFAS) to the PPARγ/RXRα-DNA Complex.

Nuclear receptors are the fundamental building blocks of gene expression regulation and the focus of many drug targets. While binding to DNA, nuclear receptors act as transcription factors, governing a multitude of functions in the human body. Peroxisome proliferator-activator receptor γ (PPARγ) and the retinoid X receptor α (RXRα) form heterodimers with unique properties and have a primordial role in insulin sensitization.

DNA preference of indenoisoquinolines: a computational approach.

The human topoisomerase IB (hTopoIB) enzyme is a monomeric protein that relaxes the supercoils on double-stranded DNA by forming a covalent DNA/hTopoIB complex by introducing a nick on the DNA strand. Inhibition of hTopoIB results in cell death, which makes this protein a strong target for the treatment of various cancer types, including small-cell lung cancers and ovarian cancers. Camptothecin (CPT) and indenoisoquinoline (IQN) classes of compounds inhibit the hTopoIB activity by intercalating to nicked DNA pairs; however, these inhibitors show different preferences towards DNA bases when bound to the DNA/hTopoIB complex.

Molecular Insights for Alzheimer's Disease: An Unexplored Storyline on the Nanoscale Impact of Nascent Aβ toward the Lipid Membrane.

Deciphering the mechanism of Alzheimer's disease is a key element for designing an efficient therapeutic strategy. Molecular dynamics (MD) calculations, atomic force microscopy, and infrared spectroscopy were combined to investigate β-amyloid (Aβ) peptide interactions with supported lipid bilayers (SLBs). The MD simulations showed that nascent Aβ monomers remain anchored within a model phospholipid bilayer's hydrophobic core, which suggests their stability in their native environment.

Investigation of iron release from the N- and C-lobes of human serum transferrin by quantum chemical calculations.

Human serum transferrin binds ferric ions with high affinity and delivers them into cells receptor-mediated endocytosis upon a decrease in pH in the endosome. Protonation events and conformational changes are known to play an important role in iron-release though the release is not yet fully understood. Human serum transferrin consists of two similar lobes which release iron at different rates.

Activity of Topotecan toward the DNA/Topoisomerase I Complex: A Theoretical Rationalization.

Topotecan (TPT) is a nontoxic anticancer drug characterized by a pH-dependent lactone/carboxyl equilibrium. TPT acts on the covalently bonded DNA/topoisomerase I (DNA/TopoI) complex by intercalating between two DNA bases at the active site. This turns TopoI into a DNA-damaging agent and inhibits supercoil relaxation.