Further investigations on the optical activity of aromatic residues in Cyclolinopeptide a analogues

CD spectra of a series of cyclolinopeptide A (CLA) analogues ([Ala¹]CLA, [Ala⁷]CLA, [Ala^1.7]CLA, [Ala⁸]CLA, [Ala⁹]CLA, [Ala⁸, Tyr⁹]CLA, [Ala⁹, Tyr⁸]CLA, and [Ala⁷, Phe(SO₃Na)⁹]CLA) in methanol solution were analyzed. It was confirmed that the aromatic residue in position 9 contributes to a low extent only to the optical activity of the peptide. However, this phenomenon is not a result of the "edge-to-face" interaction of aromatic side chains but rather of the conformation of the aromatic side chain in position 9. This conclusion is confirmed by the fact that the decrease of the optical activity in that position was also observed in the spectra of analogues with only one aromatic residue. Analysis of the CD spectra reveals also that, contrary to Leu¹, the Pro⁷ residue of the fragment -Pro-Phe-Phe-Leu-is a factor that determines the conformation of the peptide backbone and, in the consequence, the conformation of aromatic residues.