Exploring new chemical space by stereocontrolled diversity-oriented synthesis.
Natural products that act as highly specific, small-molecule protein-binding agents and as modulators of protein-protein interactions are highly complex and exhibit functional groups with three-dimensional and stereochemical diversity. The complex three-dimensional display of chiral functional groups appears to be crucial for exhibiting specificity in protein binding and in differentiating between closely related proteins. The development of methods that allow a high-throughput access to three-dimensional, skelatally complex, polycyclic compounds having few asymmetric diversity sites is essential and a highly challenging task. In the postgenomic chemical biology age, in which there is a great desire to understand protein-protein interactions and to dissect protein networking-based signaling pathways by small molecules, the need for developing "stereocontrolled, diversity-oriented synthesis" methods to generate natural product-like libraries is of utmost importance.
Arya
Prabhat
P
Chemical Biology Program, Steacie Institute for Molecular Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada. prabhat.arya@nrc.ca
Joseph
Reni
R
Gan
Zhonghong
Z
Rakic
Bojana
B
D023281:Genomics; D008958:Models, Molecular; D008968:Molecular Conformation; D009930:Organic Chemicals / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding; D013237:Stereoisomerism
D009930:Organic Chemicals