Targeting Glioblastoma Stem Cells via EphA2: Structural Insights into the RNA Aptamer A40s for Precision Therapy.

EphA2 receptor tyrosine kinase is overexpressed in many solid tumors and serves as a key driver of tumorigenesis and metastasis. It is highly expressed in glioblastoma multiforme, the most aggressive brain tumor in adults, and in its stem cells [glioblastoma stem cells (GSCs)], which contribute to treatment resistance and tumor relapse. In a previous study, we used the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) procedure, a method for selecting high-affinity nucleic acids to specific targets via iterative selection and amplification, to identify the 2'-fluorinated EphA2-targeting RNA aptamer A40L and a truncated 30-mer derivative, A40s.

Deepening bis-(thio)carbohydrazones conformational dynamics and hydrogen bond interactions in a non-protic solvent: DFT, molecular dynamics, NMR, and Raman investigations.

Despite the capability of bis-(thio)carbohydrazones to coordinate metals and the remarkable biological properties of the resulting complexes, no general information is known about their individual behavior in solution. This study is focused on two recently synthesized compounds, a bis-thiocarbohydrazone (bis-TCH) and a bis-carbohydrazone (bis-CH) isolated as sodium salts, that have shown chelating properties toward copper(II) and zinc(II) metal ions along with promising cytotoxic activity. In this work, an integrated theoretical-computational, nuclear magnetic resonance (NMR), and vibrational characterization of both bis-TCH and bis-CH anions in a non-protic solvent (dimethylsulfoxide) is presented to better elucidate their properties.

Computational Investigation of BMAA and Its Carbamate Adducts as Potential GluR2 Modulators.

Beta--methylamino-l-alanine (BMAA) is a potential neurotoxic nonprotein amino acid, which can reach the human body through the food chain. When BMAA interacts with bicarbonate in the human body, carbamate adducts are produced, which share a high structural similarity with the neurotransmitter glutamate. It is believed that BMAA and its l-carbamate adducts bind in the glutamate binding site of ionotropic glutamate receptor 2 (GluR2).

A combined approach of structure-based virtual screening and NMR to interrupt the PD-1/PD-L1 axis: Biphenyl-benzimidazole containing compounds as novel PD-L1 inhibitors.

Immunotherapy has emerged as a game-changing approach for cancer treatment. Although monoclonal antibodies (mAbs) targeting the programmed cell death protein 1/programmed cell death protein 1 ligand 1 (PD-1/PD-L1) axis have entered the market revolutionizing the treatment landscape of many cancer types, small molecules, although presenting several advantages including the possibility of oral administration and/or reduced costs, struggled to enter in clinical trials, suffering of water insolubility and/or inadequate potency compared with mAbs. Thus, the search for novel scaffolds for both the design of effective small molecules and possible synergistic strategies is an ongoing field of interest.