Month: October 2023

Maria Reinecke, Paul Brear, Larsen Vornholz, Benedict-Tilmann Berger, Florian Seefried, Stephanie Wilhelm, Patroklos Samaras, Laszlo Gyenis, David William Litchfield, Guillaume Médard, Susanne Müller, Jürgen Ruland, Marko Hyvönen, Mathias Wilhelm, Bernhard Kuster

Journal volume:pages (year)
DOI: 10.1038/s41589-023-01459-3
Pubmed: 37904048

PDB coordinates:
7zwe (3D view ), 7a4q (3D view ), 7zwg (3D view ).

Abstract

Medicinal chemistry has discovered thousands of potent protein and lipid kinase inhibitors. These may be developed into therapeutic drugs or chemical probes to study kinase biology. Because of polypharmacology, a large part of the human kinome currently lacks selective chemical probes. To discover such probes, we profiled 1,183 compounds from drug discovery projects in lysates of cancer cell lines using Kinobeads. The resulting 500,000 compound-target interactions are available in ProteomicsDB and we exemplify how this molecular resource may be used. For instance, the data revealed several hundred reasonably selective compounds for 72 kinases. Cellular assays validated GSK986310C as a candidate SYK (spleen tyrosine kinase) probe and X-ray crystallography uncovered the structural basis for the observed selectivity of the CK2 inhibitor GW869516X. Continue reading →

 Victor Bolsanelli Cioffi, Maria Fernanda de Castro‑Amarante, Aleksei Lulla, Robert Andreata‑Santos, Mario Costa Cruz, Ana Carolina Ramos Moreno, Mariângela de Oliveira Silva, Bianca de Miranda Peres, Lucio Holanda Gondim de Freitas Junior, Carolina Borsoi Moraes, Edison Luiz Durigon, Nicola Coker Gordon, Marko Hyvönen, Luís Carlos de Souza Ferreira & Andrea Balan

Scientific Reports 13: 16821 (2023)
DOI: 10.1038/s41598-023-43720-8
Pubmed: 37798298

Abstract

Amongst the potential contribution of protein or peptide-display systems to study epitopes with relevant immunological features, the RAD display system stands out as a highly stable scaffold protein that allows the presentation of constrained target peptides. Here, we employed the RAD display system to present peptides derived from the SARS-CoV-2 Spike (S) protein as a tool to detect specific serum antibodies and to generate polyclonal antibodies capable of inhibiting SARS-CoV-2 infectivity in vitro. 44 linear S-derived peptides were genetically fused with the RAD scaffold (RAD-SCoV-epitopes) and screened for antigenicity with sera collected from COVID-19-infected patients. In a second step, selected RAD-SCoV-epitopes were used to immunize mice and generate antibodies. Phenotypic screening showed that some of these antibodies were able to recognize replicating viral particles in VERO CCL-81 and most notably seven of the RAD-SCoV-epitopes were able to induce antibodies that inhibited viral infection. Continue reading →