Mechanistic insights in chiral recognition of μ-opioid receptor agonist tetrapeptide on crown ether chiral stationary phase

Abstract

Chiral separation of short peptides is of great interest, due to different pharmacological, pharmacokinetic, and/or toxicological activities often possessed by different stereoisomers of chiral drugs. Crown ether chiral stationary phases have been successfully used for separating enantiomers of various racemic compounds containing primary amino groups. Even though chiral recognition mechanism for crown-ethers CSPs is generally understood, on a molecular level, the exact chiral recognition mechanisms for the resolution are still unclear. Furthermore, short peptide analytes often contain multiple amino moieties capable of binding to the crown ether selector. A research of relationship between peptide chemical structure and chiral chromatographic interactions was performed, by comparing the retention profiles of µ-opioid receptor agonist tetrapeptide Tyr-Arg-Phe-Lys-NH2 and its structural analogues on two commercially available S- and R-(3,3’-diphenyl-1,1′-binaphthyl)-20-crown-6) stationary phases [CROWNPAK CR-I (+) and (-)], in order to clarify, which of the potential interaction sites are responsible for retention and chiral recognition in Tyr-Arg-Phe-Lys-NH2 tetrapeptide.