Related molecules, structural relationships

At the present time, use of the Fischer convention is almost entirely restricted to carbohydrates, amino acids, and biologically important molecules of closed related structural types. The problem with more general use is that there are no adequate rules for deciding whether a diiral atom is like D-glyceraldehyde or L-glyceraldehyde when the structures are not closely similar to the reference molecules. This relationship is clear for carbohydrates and amino acids. 

The logarithm for the capacity factor correlates well with known log P values obtained by the shake flask method. In practice, the k values are determined isocratically from 70 to 30% organic mobile phase and then extrapolated to 0%. Prior to determining the log P for an unknown compound, a set of structurally related molecules (standards) are analyzed to construct a correlation model between the logarithm of the retention factor and known log P values. The process is then repeated for the test compounds and their log P values determined from the mathematical relationship established for the standard compounds. 

Further studies on molecules of the type 540 (X = O, S, NR) have been described.396 y ithough the workers in this field favor a diradical representation, simple MO considerations of these molecules (540) and their close structural relationship to heteropentalenes (541) and related species... 

A theoretical model predicting the shape-structure relationship between the monomeric units and their aggregates was developed by Israelachvili and was based on statistical mechanics of phospholipids.23 This model predicts the type of the aggregate formed on the basis of the packing parameter (P), which relates the volume of the molecule (V) to its length (1) and to the mean cross-sectional (effective) head group surface area (a) ... 

Although relationships between small-molecule structures and protein families can be established on a purely empirical basis, and 3D protein-structure information is not a necessary precondition, it would be foolish not to consider such information whenever it is available. With the rapidly growing number of protein structures collated in the PDB [5], the chance of finding either the experimentally determined 3D structure of the target protein or at least one of a closely related protein that allows a sufficiently reliable homology model to be built [6] are constantly increasing. 

Sequence-comparison methods have become a powerful tool in modern biochemistry. Sequence databases can be probed for matches to a newly elucidated sequence in order to identify related molecules. This information can often be a source of considerable insight into the function and mechanism of the newly sequenced molecule. When three-dimensional structures are available, they may be compared to confirm relationships suggested by sequence comparisons and to reveal others that are not readily detected at the level of sequence alone. 

The interest in the present pharmaceutical industry is very wide spanning the overall drug discovery sphere encompassing data related to small molecules, structure activity relationships, pre-clinical candidates, clinical candidates, launched drugs, biomarkers, toxic molecules, and other target protein inhibitors. While no single database could address all these areas, attempts were made to at least address them individually. We have developed databases... 

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