Annotation of Small Molecules

NCI is asking scientists from all over the world to deposit information on the effects of small molecules on cells on the micro (gene expression) [13] and macro levels in ChemBank. One of the hopes here is to link phenotypic changes with structures and to use this information in predicting the mechanism of action of drugs. 

Kaitin (Ed,), Post-approval R D raises total drug development costs to 

2 Pharmaceutical innovation an analysis of leading companies and strategies, Reuters Business Insight 2002, can be found at http //www.delphipharma.com/ innovation.htm. 

Carlsson, P. Lindberg, Nature Rev. Drug Discov. 2003, 2,132-139. 

Fotouhi, P. Giillespie, R. Goodnow, W. Harris, P. Jones, M. Taniguchi, 

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Zhou, Y, Zhou, B., Chen, K., Yan, S.F., King, F.J., Jiang, S., Winzeler, A.E. Large-scale annotation of small-molecule libraries using pubUc databases. J. Chem. Inf. Model. 2007,47,1386-94. 

Dr. Schroeder s research aims to develop NMR spectroscopy-based approaches that complement or enhance traditional methodology by enabling detailed characterization of small molecule metabolites in complex biological samples, with regard to both chemical structure and biological function. His current work focuses on a comprehensive structural and functional annotation of the metabolome of the model organism Caenorhabditis elegans. 

The more subtle, but potentially more exciting, consequence of such multidimensional data analysis is the superposition of biological annotations onto a collection of measurements, allowing connections between the biological coordinates to be made independently of the measurements themselves. As we have seen in this chapter, there are specific relationships between various calculated molecular descriptors, based on the theory of their construction or on their relationships to molecular properties such as size and shape. Similarly, there are implicit encodable relationships between the different assays that comprise any multidimensional fingerprint of assay outcomes, such as combinations of cell states and cellular assays (Fig. 13.1-7(c)). Exploiting such relationships across diverse collections of small molecules indeed may uncover new relationships between the biological states themselves. 

Even more powerful is the notion of a global set of annotations encompassing any conceivable small-molecule assay design and allowing connections between experiments (on the same or similar compounds) conceived and performed independently in different laboratories worldwide. In their simplest form, such annotations can take the form of literature terms [132], for example,... 

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