Pi stacking is prevalent in protein crystal structures and also contributes to the interactions between small molecules and proteins
As a result, pi–pi and cation–pi interactions are important factors in rational drug design.
- Babine RE, Bender SL (August 1997). “Molecular Recognition of Proteinminus signLigand Complexes: Applications to Drug Design”. Chemical Reviews. 97 (5): 1359–1472. doi:10.1021/cr960370z. PMID 11851455.
One example is the FDA-approved acetylcholinesterase (AChE) inhibitor tacrine which is used in the treatment of Alzheimer’s disease. Tacrine is proposed to have a pi stacking interaction with the indolic ring of Trp84, and this interaction has been exploited in the rational design of novel AChE inhibitors.
- da Silva CH, Campo VL, Carvalho I, Taft CA (October 2006). “Molecular modeling, docking and ADMET studies applied to the design of a novel hybrid for treatment of Alzheimer’s disease”. Journal of Molecular Graphics & Modelling. 25 (2): 169–175. doi:10.1016/j.jmgm.2005.12.002. PMID 16413803.
Leave a Reply