At Sygnature Discovery, we thrive on solving complex protein challenges—and our recent success in solving the crystal structure of TL1A, a member of the TNF ligand superfamily, is a perfect example of how our expertise can accelerate drug discovery. Background TNF-like 1A (TL1A), also [...]

Introduction Targeted protein degradation (TPD) is an emerging therapeutic strategy that hijacks the cell’s ubiquitin–proteasome system to selectively degrade proteins. In this process, ubiquitin tags are attached to lysine residues on target proteins, marking them for destruction. A key player in this cascade is [...]

Within the Department of Protein Science and Structural Biology at Sygnature Discovery, we offer a range of eukaryotic cell lines to express recombinant protein(s). These include HEK cell lines such as HEK293-6E (on licence from the NRC, Canada) and Expi293F (on licence from Thermo [...]

In this article Jijin Ayanath describes how we at Sygnature were able to successfully identify covalent binders to a structurally challenging target. This was achieved through the development of a robust crystal soaking system, that allowed the screening of our focused covalent fragment library. [...]

STRUCTURAL BIOLOGY IN DRUG DISCOVERY In drug discovery, understanding the structure and dynamics of target proteins is essential for rational design and optimisation of therapeutic compounds. Structural biology provides the tools to achieve this, offering atomic-level insights into biomolecular interactions. Currently, X-ray crystallography, cryo-electron [...]

Post translational modifications (PTM) play a key part in protein function. One of these is glycosylation, the addition of sugar molecules to a protein by a covalent bond. There are two kinds of glycosylation seen in proteins: N-linked glycosylation and O-linked glycosylation. A further explanation [...]

The baculoviral expression vector system (BEVS) was first introduced in the 1980s. It is widely used to generate many types of protein including intracellular, secreted and membrane proteins particularly GPCRs. As BEVS is a eukaryotic system it is capable of many post translational modifications, [...]

In this case study we describe the journey to develop a process for the production of the protein component of a biopharmaceutical that was suitable for full scale manufacture. The initial laboratory scale process we were presented with was not fit for purpose and [...]

In this case study Tomas Adomavicius discusses a project where we employed various mass spectrometry techniques to confirm the target API was as expected and also to elucidate the nature of two impurity peaks that were observed during the development of a downstream process [...]

In this case study Toby Allen demonstrates the value of using multiple analytical methods to characterise Intrinsically Disordered Proteins (IDPs) and highlights some of the techniques we have available at Sygnature Discovery. What are IDPs: While many globular proteins have been characterised with a [...]