Protein druglike

Trosset J-Y, Dalvit C, Knapp S et al (2006) Inhibition of protein-protein interactions the discovery of druglike beta-catenin inhibitors by combining virtual and biophysical screening. Proteins 64 60-67... 

Another chemical property relevant to druglike behavior is stereochemistry. These are molecules that contain a chiral center (a carbon with four different attachments) causing molecules with different chiral centers to be non-superimposable. These molecules present different three-dimensional arrays to proteins, and it is presumed that this controls biological potency and efficacy. For instance, the Easson-Stedman hypothesis proposes that a biologically active enantiomer interacts with at least three points on receptor to produce biological activity. Since three points... 

Once a target-based approach is embarked upon, the choice of target is the first step. In biological systems, there are generally four types of macromolecules that can interact with druglike molecules proteins, polysaccharides, lipids, and nucleic acids. As discussed in Chapter... 

An important prerequisite for the ESI-MS/NMR assay is the appropriate design of the compound library to take full advantage of the assay s strengths. Fundamentally, the library nuxtures are prepared to contain compounds with different molecular weights, since the molecular weight is used as an identity tag to eliminate the necessity of a deconvolution step. Additional considerations include structural diversity, druglike qualities, and solubility. Typically, each well of a 96-well-plate array is prepared as a spin column, loaded with incubated protein and a mixture of 10 components, and centrifuged. 

Whilst our current knowledge may be limited in predicting a priori where uncompetitive allosteric-binding sites may appear from a protein sequence, we may be able to identify, at the sequence and structural levels, which targets are more likely to be potentially amenable to modulation by druglike small molecules from extrapolation of our current knowledge. 

---