Xtal BioStructures, Inc., (XTAL) was founded in 2005 as a Contract Research Organization (CRO) to provide numerous services to the pharmaceutical and biotechnology industries. Our focus is to provide high quality science and communication, providing our expertise in protein production and biophysical methods to enable drug screening, optimization, and development.
In order to enable proof-of concept experiments and drug discovery programs, we produce high-purity and well characterized proteins. We then provide a pipeline of affinity based biophysicial measurements for screening and drug optimization through the method of Thermal Stability Assays (TSA) and Isothermal Titration Calorimetry (ITC), and generate high resolution X-ray crystal structures. We then offer consulting and computational services on the understanding and insights that may be obtained from the perspective of the protein at a molecular level.
Our team is highly experienced and many members have been trained in multiple disciplines to provide our clients with the maximum amount of flexibility.
At XTAL, we believe that communication is a critical factor in achieving the best possible outcome. As such, we strive to develop and maintain a strong channel of open communication between our clients and ourselves throughout the process.
Epigenetics, the study of heritable changes in gene expression caused by mechanisms other than changing the DNA sequence, is a key area of research in today’s pharmaceutical industry. While many diseases and conditions may have an epigenetic component, the main focus of research is in the field of oncology.
For HTS & Structural work. XTAL has expressed and purified close to twenty bromodomain proteins. These are all well characterized and many have been crystallized. In addition to single domains, we have several tandem domains, where the activity of the protein is believed to require multiple domains.
As with any family of proteins, bromodomains have functional similarities, so it is important when developing a potential therapeutic to ensure that it is only potent, but also specific to the bromodomain target. The proteins that we have expressed include members from most of the major branches in the phylogram.
Other HDACs & the NCP
are also available. These can be more challenging proteins to prepare, especially the Nucleosome Core Particle, which is an assembly of 8 proteins with a strand of DNA wrapped around it.
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.
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.
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.
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Xtal BioStructures, Inc. has not received any endorsements.