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 [...]

BackgroundIn this case study Emma Cains describes a series of experiments that ultimately resulted in a 10-fold increase in expression with a ‘difficult to express protein’. The initial work involved comparing expression in HEK293-6E and CHO-3E7 cells, followed by the use of a high cell [...]

In this case study, Ariadna Juarez-Martinez describes how optimising the crystal system for a target protein was ultimately the key to delivering a successful fragment screen for one of our clients. 152 high-confidence fragments were identified that bound across 24 binding hotspots on the [...]

In this case study, Rachel Johnson describes how we determined the active state structure of the 5-HT2A receptor with the natural ligand serotonin bound using cryo-EM. Introduction GPCRs are a large and diverse group of receptors in the body. They are also important therapeutic targets [...]

In this Case Study Helen Gingell and Thirumalai Ulaganathan give an introduction to Fragment based drug discovery (FBDD) with a focus on using X-ray crystallography to perform FBDD. This is exemplified with a description of a project in which Sygnature Discovery ran a fragment [...]

Proximity Based Therapeutics Proximity based therapeutics have emerged as powerful tools in drug discovery and come in a wide range of different formats, including molecular glues and PROTACs (Proteolysis Targeting Chimeras). In all cases a molecule is used to bring together two cellular proteins: [...]