Editorial: The protagonism of bioanalytical methods in high-throughput drug discovery

Abstract

Protein-ligand interactions are essential for the regulation of biological processes, such as signal transduction, gene regulation, cellular metabolism, and immunoreaction. The term ligand encompasses nucleic acids, cofactors, metals, other proteins, peptides, amino acids, lipids, and drugs. Protein function can be regulated by its interaction with specific ligands through different mechanisms. Protein-ligand interaction studies are crucial for understanding the regulation of the biological function of proteins, elucidating potential biological targets, as well as discovering bioactive compounds in the drug development process. Within this context, this Research Topic aims to highlight different aspects of analytical techniques as a useful tool to develop new, rapid, and reliable ligand screening assays. Two original research manuscripts, one review, and one mini-review on analytical assays for ligand screening are collected in this Research Topic, covering assays for ornithine decarboxylase inhibitor screening, on-flow enzymatic inhibitor screening through liquid chromatography methods, liquid chromatography coupled to mass spectrometry (LC-MS) method to screen human kallikrein (KLKs) inhibitors, and a study on salt concentration to improve the separation performance of biomarkers for transporter protein inhibition. In the following paragraphs, each published manuscript is presented and briefly described. The ornithine decarboxylase (ODC) enzyme belongs to the polyamine biosynthetic pathway, catalyzing the decarboxylation of ornithine to putrescine. Polyamines (putrescine, spermidine, and spermine) are essential growth factors in eukaryotic cells, but their high levels are associated with carcinogenesis (Gerner and Meyskens, 2004) and Alzheimer’s disease (Mäkitie et al., 2010). Consequently, ODC is considered a biological target for developing new drugs for the treatment of several diseases. Tinoco et al. (2022) summarized the methods based on radiolabeling, colorimetric assays using auxiliary enzymes to detect CO2 or H2O2 release, chromatographic-based methods with putrescine derivation, mass spectrometry, circular dichroism, and fluorescence techniques. The authors highlight the demand for the development of high-throughput assays for the screening of ODC inhibitors. Since ornithine and putrescine (substrate and product) cannot be directly monitored by spectroscopic techniques, derivation or conversion procedures into spectrophotometrically detectable species are mandatory, resulting in low throughput assays. OPEN ACCESS