Heavy-atom labelling

The biological chemistry of gold a metallo-drug and heavy atom label with variable valency. P. J. Sadler, Struct. Bonding (Berlin), 1976, 29,170-214 (142). 

Sadler PJ (1976) The Biological Chemistry of Gold A Metallo-Drug and Heavy-Atom Label with Variable Valency. 29 171-214 Saillard J-Y, see Halet 1-F (1997) 87 81-110... 

DISCO considers three-dimensional conformations of compounds not as coordinates but as sets of interpoint distances, an approach similar to a distance geometry conformational search. Points are calculated between the coordinates of heavy atoms labeled with interaction functions such as HBD, HBA or hydrophobes. One atom can carry more than one label. The atom types are considered as far as they determine which interaction type the respective atom would be engaged in. The points of the hypothetical locations of the interaction counterparts in the receptor macromolecule also participate in the distance matrix. These are calculated from the idealized projections of the lone pairs of participating heavy atoms or H-bond forming hydrogens. The hydrophobic points are handled in a way that the hydrophobic matches are limited to, e.g., only one atom in a hydrophobic chain and there is a differentiation between aliphatic and aromatic hydrophobes. A minimum constraint on pharmacophore point of a certain type can be set, e.g. if a certain feature is known to be required for activity [53, 54]. 

Motto, M. Nakanishi, K. (1982) Heavy atom labeling of retinal in bacteriorhodopsin. Methods n Enzymology, vol 88, pp 178-19... 

Heavy atom-labelled inhibitors have the advantage that the specificity of the active site is exploited to generate a single site derivative. However, such reagents are likely to perturb the region of the enzyme of most interest. They have been useful in providing an approximate phase set that helps interpret a multi-site derivative and have then been discarded when the other derivatives are refined. 5-Iodouridine 2, 3 -phosphate was used in this way with ribonuclease-S [81]. 

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