Peptides

Peptides offer unique therapeutic advantages but also come with challenges requiring tailored strategies at every stage of development. Our Peptide Discovery Engine combines scientific excellence and innovative technologies to solve complex peptide drug discovery challenges, speeding up your route to clinic - saving you time and money.

Our Peptide Discovery Engine offers

This integrated peptide drug discovery service unites:

• Advanced in silico modeling
• Cutting-edge chemistry
• Tailored ADME profiling
• Rigorous biological assessments
• Adapted toxicology read outs

Whether you require a fully integrated or standalone service our Peptide Discovery Engine can be customized to meet your requirements.

Hit to lead: Identifying the best peptide lead

What sets peptide hit identification apart

Biological precision vs. chemical libraries: Small molecule hit identification relies on high-throughput screening of synthetic libraries. In contrast peptide drug discovery exploits highly ordered sequences, which can have high target affinity and selectivity

• ‍Surface Plasmon Resonance (SPR): We commonly use this method to provide rapid kinetic data, enabling precise calculation of the equilibrium dissociation constant (kd) for peptide–target interactions
• ‍Isothermal Titration Calorimetry (ITC): Is a complementary method to validate the binding strength and thermodynamics of peptide-target interactions, ensuring that our candidates bind their targets with high affinity
• ‍In silico Screening: Early computational assessments help identify potential off‑target interactions, guiding subsequent experimental validation

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Truncation and minimal pharmacophore identification: Once we’ve identified a hit—often a long peptide (>20-mer); our first step is to truncate the sequence. This helps us identify the minimal pharmacophore, the shortest active segment that retains high binding affinity and specificity

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Structural activity relationship (SAR) insights: Following truncation, we perform an alanine scan to pinpoint critical residues responsible for target binding. This systematic substitution highlights key interaction points, providing deeper insight into the structure–activity relationship

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Lead optimization: Refining potency, stability, and selectivity

How our integrated service model makes a difference

• ‍Complete data integration: We combine chemical modifications with real-time ADME profiling and biological assessments. This integrated approach ensures that our leads are not only potent but also exhibit robust stability and permeability
• Seamless collaboration: Our multidisciplinary teams—from chemists to biologists—work side by side to rapidly iterate and optimize candidate peptides, ensuring that every modification directly addresses key development challenges. Find out more about how we do achieve this in here

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The unique challenges in peptide lead optimization

Medicinal chemistry/CADD/biology

• Enhanced potency & selectivity: In small molecule development, iterative chemical modifications improve activity. For peptide drug discovery, we further refine the sequence—using insights from the alanine scan and CADD-driven modeling—to enhance both potency and selectivity

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Biology - Ensuring mode of action:

• Competitive binding assays: We can test our peptides against panels of related receptors or off‑target proteins to ensure that binding is highly specific to the intended target
• Functional cell-based assays: These assays help us determine if the peptide’s biological response is confined to the target pathway, providing further evidence of selectivity

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ADME - Overcoming metabolic and protease challenges:

Peptides face rapid enzymatic degradation, leading to a short half-life. We address this by:

• Whole blood/serum/plasma stability: Understanding the stability of peptides in ex vivo conditions
• Microsomal and hepatic profiling: Common clearance pathway for all modalities. Understanding the potential for phase I and 2 metabolism
• Protease stability testing: Characterizing metabolic soft spots through techniques like MetID
• Targeted Modifications: Incorporating D-amino acids, cyclization, and backbone modifications to improve stability, permeability, solubility, and potency

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ADME - Cell permeability and pharmacokinetic (PK) improvements:

Unlike small molecules, peptides often struggle with cell permeability. We employ chromatographic predictive oral bioavailability and permeability assessment in the form of ChamelogK evaluation and supported by cell-based permeability assays (e.g., using Caco-2 cells).

Often, permeability can be improved by:

• Applying lipophilic capping
• Modulating lipophilicity via lipid conjugation
• Incorporating peptoid or β-peptide units to enhance bioavailability
• Chameleonicity: Using analytical techniques such as EPSA and ChemelogK, we predict and optimize the dynamic conformational behavior of peptides, ensuring they perform reliably in complex biological environments
• Assessing the role of peptide transports (i.e. PEPT-1)

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Advancing the best leads toward clinical success

From lead to nomination:

Rigorous selection progress:

While small molecule nomination often relies on balancing chemical properties, peptide nomination emphasizes functional activity, stability, and safety. Our comprehensive profiling ensures that nominated leads demonstrate:

• Optimized binding kinetics
• Superior metabolic and protease resistance
• Enhanced cell permeability and favorable PK profiles

Addressing unique peptide challenges:

• Enhancing stability and bioavailability: Peptides face rapid enzymatic degradation, renal clearance, and potential immunogenicity. We improve stability through cyclization, D-amino acid substitutions, and PEGylation while increasing bioavailability via lipidation and protein conjugation
• Addressing physicochemical liabilities: Strategies like oxidation control, deamidation mitigation, and solubility optimization ensure peptides remain stable and effective. Advanced analytical techniques (e.g., LC-MS, chiral chromatography, and SEC-MALS) guide formulation refinements

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For a deeper understanding of our peptide optimization strategies, read our full blog post here.

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Throughout all this, our work is underpinned by our ability to synthesize pure, complex peptides that will return reproducible biological and ADMET data. This is clearly exemplified here.