Recent Advances in Stereoselective Drug Targeting

Reviewed here are some recent examples of medically important protein targets for which stereoselective drugs have been identified. These include heat shock protein 90 (Hsp90) inhibitors as anticancer agents; transient receptor potential vanilloid type 1 antagonists as new analgesics; stereospecific inhibition of human mutT homolog MTH1 for cancer treatment; the stereoselective binding of R‐ and S‐propranolol by the α1–acid glycoprotein transporter; metallohelical complexes that are nonpeptide α‐helical mimetics that enantioselectively target Aβ amyloid for the treatment of Alzheimer's disease; metallohelical assemblies with promising antimicrobial activity that enantioselectively target DNA of resistant bacteria; nonpeptide α‐helical metallohelices that target the DNA of cisplatin‐resistant cancer cells; diastereomeric selectivity of phenanthriplatin‐guanine adducts; and phenazine biosynthetic enzyme active sites that can host both enantiomers of a racemic ligand simultaneously. Chirality 27:589–597, 2015. © 2015 Wiley Periodicals, Inc. Recent examples of stereoselective drugs that target medically important protein targets are presented. The example shown here (with permission from JACS 2014;136:11655) depicts Fe helicates enantioselectively bound to Aβ amyloid protein associated with Alzheimer's disease.