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 [...]
Determining the Cryo-EM Structure of the 5-HT2A receptor with Serotonin Bound
Richard Mott2024-10-16T16:03:10+00:00In 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 [...]
Fragment Screening by Crystallography: An Alternative to High Throughput Screening
Richard Mott2024-10-04T20:16:13+00:00In 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 [...]
Production of Active VHL and Analysis by SPR
Peak Proteins2024-09-30T15:37:05+00:00Proximity 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: [...]
Development of a Refolding Protocol for an Interleukin
Richard Mott2024-04-30T07:37:25+00:00One of our Senior Protein Scientists, Sam Bloor, describes the journey to develop a refolding route for an interleukin. Introduction Cytokines are important cell signalling proteins which bind to cell surface receptors, initiating downstream cascades 1. They have a range of functions such as [...]
Enhancing Biotherapeutic Protein yield through CHO Expression Optimisation
Richard Mott2024-04-22T14:31:44+00:00In this case study, Emma Cains and Anna Bennett conducted a series of optimisation experiments that led to a ten-fold yield increase of a Biotherapeutic protein. Background Peak Proteins offers CHO, (CHO-3E7) HEK293-6E and HEK Expi293 expression systems for transient mammalian protein production. The [...]
Using the BacMam System in HEK293-6E cells to Generate High Level Expression of a Membrane Protein
Richard Mott2024-02-29T10:05:54+00:00In this case study Sarah Beck outlines our recent success using the BacMam system in HEK293-6E cells to generate high level expression of a GFP-tagged membrane protein required by a client on a large-scale. Introduction At Peak Proteins, as well as producing many classes [...]
The Journey To Solve a Challenging Protein Purification
Richard Mott2024-02-27T14:07:18+00:00In this case study, Toby Allen, one of our protein scientists leads us through the various steps we took to resolve a particularly tricky protein production challenge. We worked on both a full length and truncated version of a DNA binding protein and employed [...]
Using Mass Spectrometry to Rapidly Facilitate Covalent Drug Discovery
Richard Mott2024-02-27T14:07:52+00:00The Name's Bond... Covalent Bond. Covalent compounds have historically accounted for a significant number of successful drugs, but interest waned due to concerns about poor selectivity that is often identified in early assay screening. One of the key hurdles in a covalent drug campaign [...]
AlphaFold for fast structural determination of a previously unsolved domain
Richard Mott2024-09-30T13:52:02+00:00AlphaFold AlphaFold is a deep learning system, developed by DeepMind that predicts a protein’s 3D structure from its amino acid sequence. After publication in Nature in 2021, AlphaFold was subsequently used across the entire human proteome. This has since expanded to 48 organisms date which are all [...]