title: Enantiomeric separation of 2-aryloxyalkyl- and 2-arylalkyl-2-aryloxyacetic acids on a Penicillin G Acylase-based chiral stationary phase: influence of the chemical structure on retention and enantioselectivity.
abstract: 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.
authors.affiliation: Dipartimento di Chimica Farmaceutica, Università di Pavia, Via Taramelli 12, I-27100 Pavia, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Temporini
authors.forename: Enrica
authors.initials: E
authors.lastname: Calleri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fracchiolla
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carbonara
authors.forename: Fulvio
authors.initials: F
authors.lastname: Loiodice
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavecchia
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortorella
authors.forename: Gloria
authors.initials: G
authors.lastname: Brusotti
authors.forename: Gabriella
authors.initials: G
authors.lastname: Massolini
mesh_terms: D019342:Acetic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology / Q000379:methods; D004800:Enzymes, Immobilized / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D010399:Penicillin Amidase / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D011485:Protein Binding; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D002021:Buffers; D004800:Enzymes, Immobilized; D008024:Ligands; D010710:Phosphates; D010399:Penicillin Amidase; D019342:Acetic Acid