Circular dichroism study of the carbohydrate-modified opioid peptides

The conformational preferences of enkephalins and the related glycoconjugat es in which free or protected carbohydrate moieties were linked to the opio id peptides through an ether, ester or amide bond were investigated by circ ular dichroism spectroscopy in water, trifluoroethanol and water-trifluoroe thanol mixtures. The analysis of the spectra revealed that the conformation of the enkephalin molecule is very sensitive to slight changes in the pept ide structure around the C-terminal region. It was found that the type II b eta-turn structures are populated in N-terminal tetrapeptide enkephalin fra gment, while leucine-enkephalin amide feature a type I (III) beta-turn stru cture in solution. Incorporation of the sugar moiety into opioid peptide co mpound did not significantly influence the overall conformation of the pept ide backbone, although minor intensity changes may reflect shifts in the po pulation of the different turn systems. These small structural alterations can be responsible for the receptor-subtype selectivity of the various carb ohydrate-modified enkephalin analogs. (C) 1999 Elsevier Science B.V. All ri ghts reserved.