Chemical spaces ligands

Navigation in Chemical Space Ligand-based Design of Focused Compound Libraries... 

Complex optimization of the ligand-protein interactions require to scan large areas of the chemical space. Thus, the combinatorial chemist aims not at the preparation of single compounds but of chemical libraries. Chemical libraries can be produced as collections of single compounds or as defined mixtures. 

The term biology-oriented synthesis (BIOS) [45] has been used to describe the design of compound libraries based on biologically relevant chemical space [46]. The areas in protein structures that participate in productive protein-ligand interactions have been, for the most part, already defined by natural products and drugs. Thus libraries inspired by natural products and other bioactive molecules are expected to have a higher probability of biologically activity than randomly synthesized molecules [47,48]. 

Table 13.6 provides a comparison among several leading search methods in terms of their origin, search time, scope and nature of chemical space, format of input query ligand, and molecular similarity measure used. 

Bregman H, Carroll PJ, Meggers E (2006) Rapid access to unexplored chemical space by ligand scanning around a ruthenium center discovery of potent and selective protein kinase inhibitors. J Am Chem Soc 128 877-884... 

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