To discover antifungal treatments that possess the desired characteristics of 
broad spectrum activity, a strong safety profile, and oral bioavailability, new 
discovery strategies must be implemented to identify structural classes of 
molecules capable of combating these microorganisms. One such technique that has 
been implemented is the Candida albicans Fitness Test, a whole cell screening 
platform capable of delineating the mechanism of action of compounds that 
demonstrate activity against the clinically relevant pathogenic fungus, C. 
albicans. Screening crude natural product extracts with this technology has 
resulted in the identification of a novel family of antifungal natural products, 
named the parnafungins, which inhibit the enzyme polyadenosine polymerase (PAP), 
a key component of the mRNA cleavage and polyadenylation complex. Owing to the 
rapid interconversion of the structural and stereoisomers of the parnafungins at 
neutral pH, the determination of the structural isomer with the highest affinity 
for PAP with standard biochemical assays has not been possible. Herein, we 
present an application of affinity-selection/mass spectrometry (AS-MS) to 
determine that the "straight" parnafungin structural isomer (parnafungin A) 
binds preferentially to PAP compared to the "bent" structural isomer 
(parnafungin B).