Synthetic enkephalins. Addicting properties and conformational studies in solution.
The addicting properties of [Leu5]enkephalin in mice are conserved in the LSer3 analogue and lost both in the L-Ser2 analogue and in all the L-Cha4 derivatives of the above peptides. Fluorescence measurements in water show the presence of hydrogen-bonded tyrosul OH groups in [Leu5]-enkephalin and in its LSer2 analogue. The Phe4/Cha replacements do not influence these equilibria, but they affect the near u.v. dichroism of the hydrogen bonded tyrosyl residues. In the peptide absorption region in water solution, only [Leu5]-enkephalin and its cyclohexylalnyl derivative show a positive dichroism towards high frequencies, which is maintained in 8 M ura. No clear relation is found between conformation(s) in solution and biological activity. A II' beta-turn, with residues in positions 2 and 3 at the corners, is suggested for the conformation of enkephalin bound to the receptors involved in the bioassay here used.
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002942:Circular Dichroism; D004723:Endorphins / Q000138:chemical synthesis*; D004745:Enkephalins / Q000138:chemical synthesis*; D005453:Fluorescence; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D011487:Protein Conformation; D019966:Substance-Related Disorders
D000596:Amino Acids; D004723:Endorphins; D004745:Enkephalins