Abstract

Supertargeted chemistry is the study of how chemical structures localize or direct molecules to specific sub-cellular compartments in living cells. Supertargeting can be used to increase the activity or specificity of an inhibitor against its target, by concentrating the inhibitor in the particular organelle where the target is active. But, unlike structure-activity relationships, structure-localization relationships are not a simple function of compound concentration. Various aspects of mitochondrial physiology, proteomics and pharmacology have made this the organelle of choice for supertargeting studies. While exploration of supertargeting strategies to this and the other organelles has been limited, combinatorial chemical libraries of fluorescent molecules are beginning to illuminate new supertargeting mechanisms at the sub-cellular level. Moreover, predictive approaches that determine the relationship between a molecules features and sub-cellular localization are being developed in the related field of functional genomics. Applied to the small molecules, such strategies could prove useful for predicting structure-localization relationships amongst large libraries of compounds.

Keywords: supertargeting, mitochondria, endoplasmic reticulum, golgi, combinatorial chemistry, styryl, organelle, cell-based assay, high-content screening