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Novel glycosylated [Lys 7 ]‐dermorphin analogues: synthesis, biological activity and conformational investigations
Author(s) -
Biondi Laura,
Filira Fernando,
Giannini Elisa,
Gobbo Marina,
Lattanzi Roberta,
Negri Lucia,
Rocchi Raniero
Publication year - 2007
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.829
Subject(s) - dermorphin , chemistry , potency , peptide , stereochemistry , agonist , biological activity , opioid peptide , in vivo , peptide synthesis , biochemistry , receptor , in vitro , opioid , microbiology and biotechnology , biology
Syntheses of the [Lys 7 ]‐ and [Hyp 6 ,Lys 7 ]‐dermorphin analogues in which either Tyr 5 or Hyp 6 are O ‐glucosylated are described. For comparison, the carbohydrate‐free peptides have also been prepared. Structural investigations by FT‐IR and CD measurements were carried out on the synthetic analogues and some preliminary pharmacological experiments were also performed. The biological potency of the glucosylated analogues was compared with that of the µ‐opioid receptor agonist dermorphin in GPI preparations. Glucosylation of either Tyr 5 or Hyp 6 reduces the potency of both [Lys 7 ]‐dermorphin and [Hyp 6 ,Lys 7 ]‐dermorphin. The effect induced by the Tyr 5 glucosylation is quite strong and the potency of both peptides is reduced by about 150 times. A similar but less dramatic effect is induced by the glucosylation of the Hyp 6 residue, and the potency of the parent peptide is reduced by about 15 times. The presence of acetyl groups on the sugar hydroxyl functions further reduces the agonistic potency of the glucosylated analogues. The analgesic potency of [Hyp 6 ,Lys 7 ]‐, [Hyp(βGlc) 6 ,Lys 7 ]‐ and [Tyr(βGlc) 5 ,Lys 7 ]‐dermorphin were also tested in vivo by the tail‐flick test. The glucosylated hydroxyproline‐containing analogue is 8–10 times less active than the parent peptide, but its analgesic effect lasts significantly longer. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.