α-N-(S-1-phenylethyl)-β-(4’-methoxyl)benzoyl-L-alanine had been synthesized by combination of Friedal-Craft reaction and stereo-selective Michael reaction.The structure was confirmed by 1H NMR,13C NMR and X-Ray single crystal diffraction.The steady-state fluorescence property of the title compound was also investigated.It was found that the maximum emission wavelength was longer and the quantum yield was less in solvents with larger dielectric constant.The title compound displayed recognition ability to environmental state.
An unnatural amino acid, β-[6′-(N, N-dimethyl)amino-2′-naphthoyl]alanine (Ald) showing polarity-sen sitive fluorescence characteristics, was synthesized. A thorough Ald-scan of dynorphin A (Dyn A), the putative endogenous ligand for κ opioid receptors, was then performed. Replacement of the amino acid residues in positions 5, 8, 10, 12 or 14 of Dyn A(1-13)-NH2 with Ald resulted in compounds that had almost equal κ binding affinity compared with that of the parent compound; on the other hand, substi-tution of residues in position 1 or 4 with Ald decreased κ-receptor binding affinity. These results indi-cate that Tyr and Phe in Dyn A are very important for maintaining its κ-opioid activity. Evidence from receptor binding assay clearly displays that [Ald5]Dyn A(1-13)-NH2 is a highly selective κ-opioid re-ceptor agonist. An evaluation of the interaction of Ald-containing Dyn A(1-13)-NH2 analogues with SDS and DPC micelles was also performed. Interestingly, [Ald1]Dyn A(1-13)-NH2 and [Ald4]Dyn A(1-13)-NH2 showed quite different fluorescence emission maxima in SDS and DPC micelles. This indicates that both peptides are sensitive to electronic properties of the polar surface of the micelles.
