Xtal BioStructures, Inc.

Our crystallographers have many years of experience, have solved several hundred structures and use high intensity synchrotron radiation to obtain the highest resolution structural data to inform lead optimization, whether the therapeutic is a small molecule or a biologic. This experience encompasses target protein construct design, which can be a critical factor in the relevance of the data and successful solution of the structure.

Structure-Guided Drug Discovery

The co-crystal structure of a ligand-protein complex identifies the molecular interactions governing the binding of the ligand and the corresponding changes to the protein. This experimental information validates the mode of binding and provides medicinal chemists with insights that can improve the quality of the therapeutic lead.

Antibody-Antigen Structures

With the continued importance of antibodies as a therapeutic class, the structure of the antibody-antigen complex provides a definitive epitope-map. Understanding the interactions within the bound complex enables the understanding of the antibody specificity along with the design of improvements to the therapeutic by suggesting point mutations that can be made to improve the therapeutic.

Fragment Based Screens

Are becoming increasingly commonly used to identify novel and more effective pharmacophores. Identifying potential ligands to the target from a small, low molecular weight library of to the target using Thermal Shift Assays followed by determining the structure of this complex allows medicinal chemists to generate therapeutics that better interact with the target.

• Provides a complete thermodynamic profile of protein : ligand interactions
• Protein and ligand remain free of modification, tags, or coupling
• Quantitatively determines equilibrium binding affinity (Ka), binding stoichiometry, and enthalpy of binding (ΔH)
• Can determine entropy (ΔS), free energy of binding (ΔG), and dissociation constant (Kd) by extension

• Measures association and dissociation rates (ka and kd); enables calculation of the equilibrium dissociation constant (KD)
• Elucidates the interaction kinetics between a protein and its ligand
• Requires attachment of the protein or the ligand to a biosensor chip

• Measures the temperature at which a protein unfolds (Tm)
• Measures ligand-induced changes to thermal stability
• Ranks ligands by affinity, is powerful method for fragment-based screening
• Maps protein stability in various buffer conditions
• Has minimal protein requirements
• Can screen 10,000 compound per week

Our analysis of protein purity includes SDS-PAGE, Western blot analysis, mass spectrometry, size-exclusion chromatography, and a thermal stability profile. Our rigorous standards include purity at the level of sequence, quaternary structure, and post-translational modification.

Using TSA (DSF), we offer the mapping of protein stability as a function of buffer, pH, salt concentration, and additives.

We custom design purification methods to reach rigorous standards of protein purity, employing affinity-based techniques, chromatography, and refolding. We are experienced with challenging proteins, the assembly of higher order complexes, and the purification of proteins from natural sources.

We offer construct design and synthesis with codon optimization using bacterial, baculovirus, yeast, and mammalian expression systems.