Catalysis and acceleration of acyl transfer by aminocyclodextrins: a biomimetic system of use in enzyme modeling and drug design.

[formula: see text] Aminocyclodextrins (ACDs), perfunctionalized at the 6-position with amino groups, bind phosphonoformate (PFA) diesters and accelerate acyl transfer reactions with high efficiency at neutral pH. Aminolysis and esterolysis are accelerated and hydrolysis of PFA diesters is catalyzed by ACDs. PFA diesters have significant antiviral activity. The rapid reactions observed with ACDs show that biological nucleophiles may undergo facile covalent modification by PFA esters at physiological pH, which has significant implications for prodrug and drug design strategies.