RESUMEN
As we celebrate International Women's Day 2024 with the theme "Inspire Inclusion", the women of the ACS Medicinal Chemistry Division (MEDI) want to foster a sense of belonging, relevance, and empowerment by sharing uplifting stories of what inspired them to become medicinal chemists. In this editorial, we are featuring female medicinal chemistry scientists to provide role models, encouragement, and inspiration to others. We asked women medicinal chemists to contribute a brief paragraph about what inspired them to become medicinal chemists or what inspires them today as medicinal chemists. The responses and contributions highlight their passions and motivations, such as their love of the sciences and their drive to improve human health by contributing to basic research and creating lifesaving drugs.
RESUMEN
As we celebrate International Women's Day 2024 with the theme "Inspire Inclusion", the women of the ACS Medicinal Chemistry Division (MEDI) want to foster a sense of belonging, relevance, and empowerment by sharing uplifting stories of what inspired them to become medicinal chemists. In this editorial, we are featuring female medicinal chemistry scientists to provide role models, encouragement, and inspiration to others. We asked women medicinal chemists to contribute a brief paragraph about what inspired them to become medicinal chemists or what inspires them today as medicinal chemists. The responses and contributions highlight their passions and motivations, such as their love of the sciences and their drive to improve human health by contributing to basic research and creating lifesaving drugs.
Asunto(s)
Química Farmacéutica , Poder Psicológico , Humanos , FemeninoRESUMEN
In the development of therapeutics, it is important to establish engagement of a compound to its intended target and identify other targets it binds to. Methods for demonstrating target engagement in the growing field of RNA-targeted therapeutics are therefore needed. We present a detailed protocol for Photoaffinity Evaluation of RNA Ligation-Sequencing (PEARL-seq), a platform for determining interactions between small molecule ligands and their target RNA(s). PEARL-seq allows detection of binding and crosslinking events with single nucleotide resolution and allows measurement of enrichment of the target RNA relative to all other RNAs. PEARL-seq is a valuable tool in the effort to verify bona fide RNA-ligand interactions.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , ARN , Secuencia de Bases , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Ligandos , ARN/genética , ARN/metabolismo , Análisis de Secuencia de ARN/métodosRESUMEN
RNA is emerging as a valuable target for the development of novel therapeutic agents. The rational design of RNA-targeting small molecules, however, has been hampered by the relative lack of methods for the analysis of small molecule-RNA interactions. Here, we present our efforts to develop such a platform using photoaffinity labeling. This technique, termed Photoaffinity Evaluation of RNA Ligation-Sequencing (PEARL-seq), enables the rapid identification of small molecule binding locations within their RNA targets and can provide information on ligand selectivity across multiple different RNAs. These data, when supplemented with small molecule SAR data and RNA probing data enable the construction of a computational model of the RNA-ligand structure, thereby enabling the rational design of novel RNA-targeted ligands.