Biology-oriented synthesis.
Which compound classes are best suited as probes and tools for chemical biology research and as inspiration for medicinal chemistry programs? Chemical space is enormously large and cannot be exploited conclusively by means of synthesis efforts. Methods are required that allow one to identify and map the biologically relevant subspaces of vast chemical space, and serve as hypothesis-generating tools for inspiring synthesis programs. Biology-oriented synthesis builds on structural conservatism in the evolution of proteins and natural products. It employs a hierarchical classification of bioactive compounds according to structural relationships and type of bioactivity, and selects the scaffolds of bioactive molecule classes as starting points for the synthesis of compound collections with focused diversity. Navigation in chemical space is facilitated by Scaffold Hunter, an intuitively accessible and highly interactive software. Small molecules synthesized according to BIOS are enriched in bioactivity. They facilitate the analysis of complex biological phenomena by means of acute perturbation and may serve as novel starting points to inspire drug discovery programs.
Max-Planck-Institut für Molekulare Physiologie, Abt. Chemische Biologie, Dortmund, Germany.
Stefan
S
Wetzel
Robin S
RS
Bon
Kamal
K
Kumar
Herbert
H
Waldmann
D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry
D001688:Biological Products; D004791:Enzyme Inhibitors; D011506:Proteins; D054852:Small Molecule Libraries