Influence of amino acid residue on chromatographic behaviour of μ-opioid receptor agonist tetrapeptide analogue on crown ether based chiral stationary phase

Abstract

The influence of amino acid residue on μ-opioid receptor agonist tetrapeptide Tyr-Arg-Phe-Lys-NH2 analogue chromatographic behaviour on crown ether based chiral stationary phases has been investigated. S- and R-(3,3′-diphenyl-1,1′-binaphthyl)-20-crown-6 chiral selectors in commercially available CROWNPAK CR-I (+) and (-) columns are both each other enantiomers, thus, under the same LC conditions, retention of Tyr-Arg-Phe-Lys-NH2dxxx enantiomers (fixed in d-tyrosine position) on S-chiral selector do not significantly differ from the retention times of their lxxx antipodes, obtained on R-chiral selector (and vice versa), allowing us to study the apparent separation of a specific tetrapeptide enantiomeric pair, without obtaining the actual racemate. Ten tetrapeptides (llll-isomers) have been synthesized with the aim to cover a wider range of different amino acid classes. Histidine, glutamic acid, cysteine, leucine and tryptophan were introduced at the N-terminus or Phe position of Tyr-Arg-Phe-Lys-NH2 tetrapeptide structure. The effects of the amino acid residue with emphasis on retention, enantioseparation, as well as the influence of position of the amino acid residue in tetrapeptide sequence, are discussed.