Creative Biostructure offers high-throughput and high-quality UniCrysTM crystallization services by using state-of-the-art facilities and technologies in the field of X-ray Crystallography, and has developed a crystallography pipeline including all the stages from gene synthesis to structure determination. Our experienced scientists can teamwork with customers and accelerate the research progress.
A crystal structure is formed by atoms, ions or molecules in a highly ordered crystalline liquid or solid. As crystalline atoms are able to cause the X-rays diffraction, the crystal structure can be determined by measuring the angles and intensities of these diffractions. Since the first determined protein structure –Myoglobin –in 1958, X-ray Crystallography has become the most significant and useful tool for protein structure determination. Nowadays, more than 111,000 protein structures have been deposited into the Protein Data Bank and about 90% of them are by X-ray, suggesting its overwhelming advantages in protein structure study.
The key step in X-ray Crystallography is the crystallization process. Since each protein has its unique physical and chemical properties, the initial crystallization screening can be very costly and time consuming. However, by taking advantages of hundreds of non-redundant crystallization conditions and multiple crystallization approaches (such as vapor diffusion crystallization, seeding and co-crystallization), Creative Biostructure can provide the most efficient and economical strategies. To obtain high-resolution protein structures, both in-house X-ray facility (for trial and optimization) and synchrotron light source (for data collection) will be used. High-resolution X-ray data, high-quality density maps, protein structures and statistics will also be made available for the purpose of publication and subsequent studies.
The quality of the final crystal product is defined in terms of its purity, polymorphic and size distributions, habit and morphology, residual solvent and crystal mechanical strength. These properties can be controlled either by proper selection of the process variables such as the solvent type, the degree of local and average supersaturation, degree of mixing (macro-, meso- and micro-mixing), crystallizer geometry, and seeding policy (loading, dry or slurry form, time of addition, etc.), or by implementing external control.
Applications of the crystallization process in the pharmaceutical industry
Crystallization from the solution is an old process that has various diverse and useful applications in the pharmaceutical industry. It was demonstrated that the crystal properties of active pharmaceutical ingredients (APIs) prepared by crystallization may be controlled either by proper selection of process variables such as the geometry of the crystallizer, the degree of mixing, solvent type, seeding policy, etc., or by implementation of external control in the form of feedback or optimal control. Formation of theophilline-nicotinamide co-crystals by grinding or slow evaporation to enhance bioavailability of theophilline was demonstrated. Two methods, micro-crystallization and the use of magnetic nanoparticles, were introduced for the preparation of progesterone for pulmonary administration. What’s more, single crystal information in the resolution of chloro-mandelic acid by ethylphenylamine confirmed the importance of the CH/π interactions and van der Waals forces between the less soluble and the more soluble salts when hydrogen-bonding exhibits identical features in systems for successful resolution.
Custom UniCrys™ X-ray Crystallography Services:
The structural biology team at Creative Biostructure carries out high-resolution structure determination by X-ray crystallography to support both stand-alone and integrated drug discovery projects. We have access to both in-house and synchrotron data collection facilities to provide fast turnaround and high-throughput structure determination (including fragment screening campaigns).
Rohani S, Horne S, Murthy K S K. Control of the product quality in batch crystallization of pharmaceuticals and fine chemicals. Part 1: design of the crystallization process and the effect of solvent. Org Res Proc Dev, 2005, 9(6): 858–872
Rohani S, Horne S, Murthy K S K. Control of the product quality in batch crystallization of pharmaceuticals and fine chemicals. Part 2: external control. Org Res Proc Dev, 2005, 9(6): 873–883