Temporini Caterina, Calleri Enrica, Fracchiolla Giuseppe, Carbonara Giuseppe, Loiodice Fulvio, Lavecchia Antonio, Tortorella Paolo, Brusotti Gloria, Massolini Gabriella
Dipartimento di Chimica Farmaceutica, Università di Pavia, Via Taramelli 12, I-27100 Pavia, Italy.
J Pharm Biomed Anal. 2007 Oct 18;45(2):211-8. doi: 10.1016/j.jpba.2007.06.005. Epub 2007 Jun 12.
The chiral recognition mechanism of Penicillin G Acylase (PGA) was investigated with a set of 18 new chiral acidic compounds. A series of 2-aryloxyalkyl- and 2-arylalkyl-2-aryloxyacetic acids in which the absolute configuration has been reported to exert a strong influence on pharmacological activity, were synthesized and analysed on PGA-based chiral stationary phase (CSP) and 11 racemates were completely resolved with a mobile phase composed of 50 mM phosphate buffer (pH 7.0). The influence of structural variations of analytes on retention and enantioselectivity was investigated by application of molecular modelling studies. Docking experiments were also carried out to rationalize the observed enantioselective behaviour. The computation approach revealed to be helpful in elucidating the molecular basis of the enantioselectivity observed on PGA-CSP.
