Why is it necessary to analyze glycan thermodynamics in addition to simple binding assays?

Simple binding assays (like ELISA) give you a single number for affinity. Our thermodynamic analysis goes deeper, revealing why a certain molecule binds with a particular affinity. This allows for rational design by uncovering the specific energetic contributions of enthalpy and entropy, which helps you fine-tune your molecules for optimal performance.

How does this service compare to other glycan analysis methods like mass spectrometry?

Mass spectrometry is excellent for identifying glycan structures and compositions, which is a crucial first step. Our service is a perfect complement, as it answers the next critical question: "How does that structure affect its functions and stability?" We provide the functional and biophysical data that mass spectrometry alone cannot.

What is the typical turnaround time for this service?

The timeframe for our service is project-specific, generally ranging from 8 to 12 weeks. Factors such as sample complexity, the number of glycoforms to be analyzed, and the specific assays required can influence the duration. We will provide a detailed project plan and timeline after your initial consultation.

Glycan Crystal Thermodynamic Analysis Service

How Creative Biolabs' Glycan Crystal Thermodynamic Analysis Service Can Assist Your Project

Reliable crystal thermodynamic analysis service. (Creative Biolabs AI)

Facing challenges with long drug discovery cycles or the high costs of biopharmaceutical production? Our One-Stop Glycan Crystal & Glycoprotein Crystal Analysis Services is your solution. We help you accelerate drug development and obtain high-quality, highly specific antibodies by providing deep insights into glycan-protein interactions. Using advanced biophysical methods, we analyze the thermal stability and Binding Dynamics of your therapeutic products, paving the way for more effective and rationally designed drugs. At Creative Biolabs, our glycan crystal thermodynamic analysis service provides critical data on the conformational stability and binding mechanisms of your glycan-containing molecules. By precisely measuring the energy and dynamics of these interactions, we help you understand why one glycoform performs better than another, enabling you to optimize your therapeutic candidates. Our service goes beyond simple binding assays to deliver the foundational physicochemical data needed for informed decisions in drug design and formulation.

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Glycosylation is a critical post-translational modification that dictates the functions and stability of many proteins. Glycans, once thought to be rigid, are now understood as dynamic structures that exist in a conformational equilibrium. This newfound understanding has revolutionized the field of glycobiology, revealing that subtle changes in carbohydrate structure can profoundly impact a molecule's binding affinity and therapeutic efficacy. Our service provides the tools to measure and understand these intricate interactions, which are essential for the rational design of new therapeutics.

The primary challenge in glycan analysis has always been the complexity of carbohydrate structures and their dynamic nature in solution. Traditional methods often fail to capture the subtle but significant conformational and thermodynamic properties that are critical for biological function. Our service is designed to overcome these challenges by providing a comprehensive suite of analytical services. Our service is a multi-step, integrated process that combines state-of-the-art technology with expert analysis.

Sample Preparation

Clients submit their samples, which can include purified glycoproteins, glycopeptides, or even crude extracts. Our team performs a preliminary analysis to confirm sample quality and prepare it for analysis.

Thermodynamic Characterization

We employ a range of powerful biophysical techniques to characterize your molecules.

Differential scanning calorimetry (DSC): This method measures the thermal stability and folding properties of your molecule. By analyzing the melting point (Tm), heat capacity (Cp), and enthalpy (ΔH), we can determine how stable your glycan-protein complex is and how it responds to temperature changes.
Isothermal titration calorimetry (ITC): ITC is the gold standard for characterizing molecular interactions in solution. It directly measures the heat exchanged when two molecules bind, providing a complete thermodynamic profile of the interaction, including binding affinity (Kd), the energetic contributions of enthalpy (ΔH), and entropy (ΔS). This data is crucial for understanding whether a binding event is driven by hydrogen bonds (enthalpy) or conformational changes (entropy).

Binding Kinetics Analysis

While thermodynamics tells us about the overall energy of binding, kinetics tells us how fast the binding and unbinding occur. We use surface plasmon resonance (SPR) to measure the real-time association and dissociation rates of your molecules. This provides a more complete picture of the interaction and can reveal subtle differences in binding behavior between different glycoforms.

Molecular and Statistical Modeling

The raw data from DSC, ITC, and SPR are used to inform and validate computational models. We use our expertise in molecular dynamics (MD) simulations to visualize the conformational equilibrium of your glycans and predict how they interact with their binding partners.

Data Integration and Report Generation

All data points from our experiments and models are integrated into a single, comprehensive report. This is not just raw data, but a narrative that explains what the results mean for your project. We provide actionable insights and recommendations, allowing you to move forward with confidence.

The Necessity of This Service

The necessity of a glycan crystal thermodynamic analysis service stems from the fact that a drug's efficacy and safety are directly tied to its glycan structure. Without a deep understanding of these interactions, drug development is a trial-and-error process, leading to increased costs and prolonged timelines. This service is essential for:

Published Data

This scientific article explores how the N-glycan sugar molecules attached to a therapeutic antibody's Fc region influence its function. The study introduces a novel chromatography column using an engineered FcγRIIIa receptor to separate different antibody variants based on their glycan composition, successfully isolating a model antibody into three distinct fractions. A central finding is the direct link between the amount of galactose on the antibody's glycan and its binding affinity to the FcγRIIIa receptor, with higher galactose content resulting in stronger binding and, consequently, a more potent immune response. To uncover the molecular basis for this, the researchers performed a detailed thermodynamic analysis.

The data highlighted in the Figure is crucial for explaining this mechanism. The researchers used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to measure the flexibility of the antibody's structure. Their results show that a specific peptide segment within the Fc domain becomes more flexible as the galactose content decreases, which is depicted by a higher deuterium uptake in the figure. The study further reveals through thermodynamic analysis that the presence of galactose is associated with a more favorable entropy change during binding. This suggests that galactose reduces the conformational entropy of the antibody, leading to a more rigid structure. In turn, this reduced flexibility facilitates a more optimal and robust binding interaction with the FcγRIIIa receptor. Therefore, the paper confirms that subtle variations in the glycan profile significantly impact the antibody's thermodynamic behavior, which is a primary determinant of its biological effectiveness.

Kinetic and thermodynamic analysis of antibodies with different glycosylation forms. (OA Literature)

Fig.1 Dynamic and thermodynamic behavior of IgG-Fc with different glycosylation forms.¹

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Creative Biolabs provides a distinct advantage by combining cutting-edge biophysical analysis with a deep understanding of glycobiology. Our expertise in Glycan Crystal and Glycoprotein Crystal Analysis allows us to uncover the underlying mechanisms of glycan-protein interactions. The integration of advanced molecular modeling with experimental data provides a holistic view of your molecule's behavior. Our glycan crystal thermodynamic analysis service is a powerful tool for gaining a competitive edge in the complex world of glycobiology. Please contact our team to discuss your project and learn how our expertise can help you achieve your goals.