Abstract: The present invention relates to the field of affinity purification and provides for means and methods applying protein binding agents competing for a target protein for use as capture and elution tool, wherein the elution agent comprises an immunoglobulin single variable domain (ISVD), and is capable of displacing the capturing binding agent. More specifically, the displacement efficiency of the ISVD-containing protein binding agent is driven by its dissociation kinetics, with a rate constant of dissociation (koff) equal or lower as compared to the capturing agent. Furthermore, said protein binding agents are deployable in high-throughput purification from complex mixtures, or for capturing protein-complexes, thereby facilitating structural, biochemical and physicochemical analysis of said target proteins.

Abstract: The present invention relates to non-naturally occurring antibodies or active antibody fragments specifically binding the calcium-sensing receptor (CaSR), acting as positive allosteric modulators (PAMs) to provide for potent therapeutic agents. More particular, the immunoglobulin single variable domains (ISVDs) identified herein reveal a novel therapeutic strategy to reduce parathyroid hormone release in a subject, and are therefore suitable for treatment of hypercalcemia disorders. Moreover, co-application of such an ISVD and a synthetic PAM or calcimimetic results in a synergistic agonistic CaSR activity providing for pharmaceutical compositions as next generation CaSR drugs.

Abstract: The present invention relates to the field of structural biology. More specifically, the present invention relates to novel fusion proteins, their uses and methods in three-dimensional structural analysis of macromolecules, such as X-ray crystallography and high-resolution Cryo-EM, and their use in structure-based drug design and screening. Even more specifically, the invention relates to a functional fusion protein of a cytokine and a scaffold protein wherein the scaffold is a folded protein that interrupts the topology of the cytokine to form a rigid fusion protein that retains its receptor binding and activation capacity. More specifically, chemokine- and interleukin-based functional fusion proteins, and their production and uses, are disclosed herein.

Abstract: The application relates to the field of structural biology. More specifically, the disclosure relates to methods for the identification and characterization of biomolecular tools allowing the selective recognition and/or stabilization of distinct conformational states of protein complexes, including transient protein-protein interactions and protein-nucleic acid complexes. Such tools can then be used for purification purposes, crystallization and structure determination of these stabilized protein complexes, for drug discovery, as research tools, as well as for diagnosis and treatment of diseases.

Abstract: The application relates to the field of structural biology. More specifically, the disclosure relates to methods for the identification and characterization of biomolecular tools allowing the selective recognition and/or stabilization of distinct conformational states of protein complexes, including transient protein-protein interactions and protein-nucleic acid complexes. Such tools can then be used for purification purposes, crystallization and structure determination of these stabilized protein complexes, for drug discovery, as research tools, as well as for diagnosis and treatment of diseases.