Protein crystallography has become a mainstream analytical method in assisting the pharmaceutical chemistry field. Specific work on proteases which are instrumental in lead compound discovery have blossomed over the passed two decades as the need for Co-crystallization of target proteins with small molecules is seeing a drastic increase now that their uses in drug design have become fully apparent. Work on phosphorous cleaving and donating enzymes (Kinases and phosphatases) has also become an area of current interest as potential cancer therapy by affecting the energy yield in a cancer cell through interruption of ATP generation. “The use of protein crystallography is highly influential in structure-guided drug design as researchers can help determine the absolute stereochemistry of a compound and alter it if necessary to favour the necessary binding conformation”3.
Co-crystals:
Pharmaceutical Relevance:
Co-crystals have come up in pharmaceutical chemistry as an important and controversial topic. Although there is disagreement on the definition of what is classified as a co-crystal, their importance in pharmaceutical chemistry and X-ray crystallography is noted. Co-crystals are believed to be a crystalline structure of at least two components composed of atoms, molecules or ions. These components form a single unique crystalline structure and have proven to be quite beneficial in vitro as a medicinal delivery system.
Pharmaceutical Advancement:
Several advances on the design, growth and characterization of co-crystals have increased exponentially over the past several decades. It has only been in the past several years however, that reference to pharmaceutical chemistry has begun to flourish as the discovery that ...
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...ghout all stages of the discovery process. “One such computational approach that can go hand-in-hand with major phases of drug discovery such as “hit identification” and “hit-to-lead”; the initial phase involves the identification of a list of chemical compounds, known as ‘hits’, that ideally exhibit some degree of potency and specificity against the target. Whereas, the latter engages evaluation of the screened hits to identify the promising lead molecules before proceeding toward a large-scale lead optimization”7. With drug design rapidly turning into a science of discovery time reduction and results a conglomerate of different methods are being pooled together to assist in “hit identification”. The use of bioinformaticians, systems biologists, and computational clustering methods has allowed researchers validate desired biological targets at a lightning pace.
The ultimate goal of pharmacogenomics, as stated by Henig, “would be for everyone’s genome to be analyzed indi...
Fully describes the crystallochemical relationships between the structures and the temperature dependence of polymorphism. )
The IR spectrum that was obtained of the white crystals showed several functional groups present in the molecule. The spectrum shows weak sharp peak at 2865 to 2964 cm-1, which is often associated with C-H, sp3 hybridised, stretching in the molecule, peaks in this region often represent a methyl group or CH2 groups. There are also peaks at 1369 cm-1, which is associated with CH3 stretching. There is also C=O stretching at 1767 cm-1, which is a strong peak due to the large dipole created via the large difference in electronegativity of the carbon and the oxygen atom. An anhydride C-O resonates between 1000 and 1300 cm-1 it is a at least two bands. The peak is present in the 13C NMR at 1269 and 1299 cm-1 it is of medium intensity.
To form an ice crystal you need a structure that can be repeated periodically (ESRF). This is not possible with five-fold coordinated groups. In a ...
Non – competitive inhibitors change the globular shape of an enzyme so that a enzyme-substrate complexes can’t form meaning a lower optimum rate of reaction. Enzymes in Medicine = == ==
For a drug to get to market it must go through several stages of research and development (Abbott and Vernon). Starting with discovery research, preclinical testing on animals, three phases of clinical trials on humans, and finally FDA (Food and Drug Administration) approval (Abbott and Vernon). Out of several thousands of drugs only a few will make it to the FDA approval stage (Abbott and Vernon). Testing is a highly regulated, time consuming, and expensive process. From beginning to end the process can take fifteen years and less than one of five compounds will make it to market where it is still not guaranteed to succeed (Abbott and
The conical vial was placed in a small beaker and allowed to cool to room temperature. The mixture was Cooled thoroughly in an ice bath for 15-20 minutes and crystals collected by vacuum filtration on a Hirsch funnel. The vial was rinsed with about 5 mL of ice water and transferred into to the Hirsch funnel and again washed with two additional 5mL portions of ice water. Crystals were dried for 5-10 minutes by allowing air to be drawn through them while they remained on the Hirsch funnel. The product was transferred to a watch glass plate and allow the crystals to dry in air. Crude acetaminophen product was weighed and set aside a small sample for a melting point determination and a color comparison after the next step. Calculation of the percentage yield of crude acetaminophen (MW = 151.2). was done and recorded in the lab notebook.
David and John Free. (26 Nov 2006). MadSci Network: Chemistry. Retrieved on March 6, 2011, from http://www.madsci.org/posts/archives/2007-02/1171045656.Ch.r.html
23. S. Alwarappan, S. Boyapalle, A. Kumar, C.-Z. Li and S. Mohapatra, J. Phys. Chem. C, 2012, 116, 6556–6559
Nexium is a delayed-released capsule that is composed of S-5-methoxy-2-[(4-methoxy 3, 5-dimethylpyridin-2-yl) methylsulfinyl]-3H-benzoimidazole.7 The chemical formula for esomeprazole magnesium trihydrate is (C17H18N3O3S) 2Mg. 3H2O. The three water molecules show that esomeprazole magnesium trihydrate is slightly soluble in water.7 Esomeprazole salt is the S-enantiomer of omeprazole which contains both S and R-isomers.7 The S-isomer is active as it is attached to four different compounds meanwhile the R-isomer is inactive. The chiral center of the S-isomer is the sulfur which is located in the middle of the compound bonded to two carbon atoms on either side of the sulfur. The sulfur also has a double bonded oxygen atom, and two lone pairs of electrons indicating that it has a tetrahedral bond angle hence chirality.11
More than 45 million chemical compounds are known and the number may increase in million every year, without cheminformatics, the access of these huge amounts of information is very difficult.
During the past two decades significant research effort has been made to develop a better understanding of the crystallization mechanisms like nucleation, growth etc, as well as on the modeling and control of crystallization systems. The advancement in process analytical technology and computing power has made this task much easier. The key developments have occurred in novel crystallization concepts, modeling, monitoring and control. A major development in the modeling area is the use of multi-dimensional population balance models which gives the morphological model of crystallization processes, as well as in the better understanding of crystallization in impure media. Developments in...
"Within a single subunit [polypeptide chain], contiguous portions of the polypeptide chain frequently fold into compact, local semi-independent units called domains." - Richardson, 1981
Plontke, R. (2003, March 13). Chemnitz UT. TU Chemnitz: - Technische Universität Chemnitz. Retrieved April 1, 2014, from http://www.tu-chemnitz.de/en/
Ionic compounds, when in the solid state, can be described as ionic lattices whose shapes are dictated by the need to place oppositely charged ions close to each other and similarly charged ions as far apart as possible. Though there is some structural diversity in ionic compounds, covalent compounds present us with a world of structural possibilities. From simple linear molecules like H2 to complex chains of atoms like butane (CH3CH2CH2CH3), covalent molecules can take on many shapes. To help decide which shape a polyatomic molecule might prefer we will use Valence Shell Electron Pair Repulsion theory (VSEPR). VSEPR states that electrons like to stay as far away from one another as possible to provide the lowest energy (i.e. most stable) structure for any bonding arrangement. In this way, VSEPR is a powerful tool for predicting the geometries of covalent molecules.