Using Structure to Understand Common Bioisosteric Replacements

Using Structure to Understand Common Bioisosteric Replacements 

Biososteres derived from tacit medidnal chemistry knowledge or pairwise analysis methods do not always take account of the nature of the hrnding pocket containing 

In the Pfizer in-house IC50 data set, there are 1059 pairs of compounds consisting of a carboxylic add and the equivalent tetrazole that have been tested in the same assay. In order to define a binding environment for the acid/tetrazole, an attempt was made to map each pair to its most relevant pocket in the PDB ligand database by identifying the most similar cocrystallized ligand in a protein from the same family. 

Rodgers, f.R., Kennard, O., Shimanouchi, T, and Tasumi, M. (1977) The Protein Data Bank a computer-based archival file for macromolecular structures. Journal of Molecular Biol , 112, 535-542. 

Berman, H.M., Westbrook, f., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., and Bourne, P.E. (2000) The Protein Data Bank. Nucleic Acids Research, 28, 235-242 www.pdb.org. Leach, A.R., Gillet, V.J., Lewis, R.A., and Taylor, R. (2010) Three-dimensional pharmacophore methods in drug discovery. Journal of Medicinal Chemistry, 53 (2), 539-558. 

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Using Structure to Understand Common Bioisosteric Replacements 179... 

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