Biophysics
At Sygnature Discovery, we see biophysics as a core component of drug discovery projects, which can generate data throughout the pipeline. From hit finding and target engagement studies, to the characterisation of kinetic properties for late-stage candidate molecules, we believe that a biophysical approach complements other assays to deliver a fuller picture of binding behaviour to produce more effective therapeutics.
Biophysics in Drug Discovery: A Sygnature Approach
Our key biophysics leaders alone possess over 50 years of combined experience in drug discovery, spanning CRO, pharmaceutical, and biotech sectors, and applied across various target classes and therapeutic modalities. This wealth of experience supports our broader team of over 20 scientists, each trained in at least one biophysical technology.
We advocate a collaborative approach, engaging both with our clients and within our internal team. This ensures that full access to our collective experience is a standard feature of all projects, regardless of their size or scope—be it large, multi-disciplinary projects or specific biophysics-only projects designed to complement work with other scientific partners. Leveraging this extensive pool of knowledge and experience enables us to succeed in projects where others may not.
Our preferred working method involves assigning dedicated scientists exclusively to your project. We believe this approach yields the best results in terms of quality, output, and communication. However, in some instances, this method may not be suitable due to the project’s scale or uncertain timelines. In such cases, our dedicated team is prepared to undertake work on a fee-for-service basis, accommodating smaller or more segmented projects.
Comprehensive Assay Development for Diverse Applications
Our team here at Sygnature Discovery, comprised of expert biophysicists, is highly experienced in a variety of target classes and drug modalities. We are adept at designing biophysical assays for complex targets, utilising a comprehensive range of options to create the most fitting biophysical assay for each specific target system.
Diverse Target Classes We Work With:
- Soluble Proteins: This includes kinases, ligases, transcription factors, helicases, polymerases, and DNA/RNA modifying enzymes, among others.
- Membrane Proteins: Examples include cell surface receptors, GPCRs, and transporters.
- Nucleic Acid Targets: Focusing on specific interactions and functions.
Sygnature Discovery’s Biophysical Assay Development Capabilities:
| 1. Small Molecule Binding Assays | · Fragment Screening
· HTS Hit Validation · Virtual Screen Hit Confirmation · DEL Screening Hit Validation · Affinity/Kinetic Determination (lead identification/lead optimisation) |
| 2. Antibody Characterisation | · Kinetic Characterisation
· Epitope Binning |
| 3. Ternary Complex Formation Assays | · Full PROTAC and Molecular Glue Characterisation
· Cooperativity Assessment · Pre-developed Assays with Key Ligases |
| 4. Protein-Protein Interaction (PPI) Assays | · Binding Characterisation
· PPI Inhibition Assays |
| 5. High Affinity Binding Assays | · Chaser Assays
· Sub pM KD determination |
| 6. Covalent Hit Characterisation | · Hit Validation/Triage following hit finding.
· Covalent Characterisation (including KI and kinact) |
| 7. Peptide Binding | · Linear and Macrocyclic peptides |
| 8. Assessment of Toxic Payload Molecules | · Precursor Molecules
· Conjugated Molecules · Link from biophysical techniques to cellular potency and effect |
Why Choose Biophysics for Target Analysis at Sygnature Discovery?
Selecting the is highly target-dependent and will be guided both by what works for the target and by what the needs of the project are.
- Do you need kinetic analysis or easy-to-read detail on stoichiometry? SPR is likely the best technique.
- Are you working with very weak binders or need to get some initial binding site information? NMR has several advantages in this space.
- Do you need affinity data for a protein that doesn’t tolerate capture on a sensor surface? MST may be for you.
At Sygnature Discovery, we keep all the options open to allow for the most effective approach for your target, often employing multiple technologies in parallel to get the best possible results, even for complex systems.
Scaling Biophysics for Enhanced Project Support at Sygnature
At Sygnature Discovery, we have made significant investments in biophysics, both in expert skills and state-of-the-art equipment, to comprehensively support our clients’ projects. Our capabilities allow us to conduct biophysics on a large scale when needed, and quickly evaluate multiple technologies to identify the most effective assay readouts. Our current suite of advanced instrumentation includes:
- 6x Biacore
- 1x High throughput Monolith NT.Auto for MST
- 2x 384-well instruments for DSF/FTSA
- 2x NMR magnets for 19F ligand observed NMR
- Mass-spectrometry for a range of applications (ligand binding studies, enzyme assay readouts and more!)
Additionally, we’ve established strong partnerships with external providers to further expand our capabilities. This includes access to:
- Access to additional NMR instrumentation for 1H ligand observed NMR (600 MHz, low volume, cryoprobe equipped)
- ITC
These resources enable us to offer a comprehensive range of biophysical techniques, ensuring precise and efficient project advancement.
At Sygnature Discovery, biophysics is integral to our drug discovery process, providing detailed insights from hit finding to late-stage candidate characterisation. Our extensive resources, including advanced equipment and expert collaborations, ensure tailored, effective strategies for each unique project.