Drug design process

Taghavi-Moghadam, S., Kleemann, A., Golbig, K. G., Microreaction technology as a novel approach to drug design, process de-... 

Once a homology model of a receptor and the ligand structure are available, the ligand can be docked into the receptor. This procedure has been widely used in the structure-based drug design process to screen... 

Many large proteins exert biological activity of pharmaceutical interest. In the drug design process the biological activity is often associated with an interaction mediated by certain residues or domains. Peptides made from these residues or domains often exhibit the same activity and can be used to derive novel compounds. 

Aqueous solubility is typically inversely proportional to lypophilicity. Lypophilicity represents the affinity of a molecule (or moiety) for a lypophilic environment. Dmg solubility is also an important attribute to its oral absorption and subsequent permeability through membranes. In medicinal chemistry, solubility for a 1-mg kg dose of 5,50, and 500 p,g mL is estimated to be low, medium, and high, respectively (Van de Waterbeemd, 2002). Solubility characteristics have long been recognized as important in pharmaceutical chemistry and are part and parcel of the drug design process. For example, the solubility can be used to determine the maximal absorbable dose (MAD), that is. 

Once the NMR spectra of a peptide are assigned the range of techniques mentioned earlier can be used to retrieve information that is valuable in the drug-design process. Clearly the 3D structure of the peptide is of vital importance, and we examine it first. Indeed, as is illustrated in Fig. 4, the assignment and structure determination processes are often completed together. 

We now turn to an examination of a range of NMR methods for studying intermolecular interactions relevant in the drug-design process. 

Structural diversity of the studied ligands. If one considers these circumstances, important information can be obtained from a comparison of the contour maps and the binding site, vhich can then be integrated in the drug design process. 

It is out of the scope of this book to demonstrate practical case histories for the application of molecular descriptors in the drug design process but we have had some very promising preliminary results. 

The results presented have demonstrated the ability of silicon diols to have serine protease inhibitory activity. The silicon diol 9 is a potent human leucocyte elastase inhibitor. The fact that the silicon diol moiety can be used across the aspartyl, metaJlo, and serine gene mily of proteases shows the power of such a simple privileged structure within the drug design process. 

Compounds with reactive functional groups are avoided, whenever possible, during the drug design process. Formation of reactive metabolites has... 

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