ISSN:
1075-2617
Keywords:
enkephalins
;
DPDPE
;
opioid agonists
;
δ-receptor
;
fluorine containing amino acid
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Analogs of Met-enkephalin and [d-Pen2, d-Pen5]enkephalin (DPDPE) containing the partially fluorinated amino acid 4,4-difluoro-2-aminobutyric acid (DFAB) in the 2- or 3-position of the peptide sequence were synthesized and their opioid activities and receptor selectivities were determined in vitro. The linear fluorinated [d-DFAB2, Met5-NH2]enkephalin showed μ and δ agonist potencies comparable to those of natural [Leu5]enkephalin. The partially fluorinated DPDPE analogs behaved differently as compared with their non-fluorinated correlates. While l-amino acid substitution in position 3 of DPDPE usually resulted in higher δ agonist potency than d-amino acid substitution, [d-DFAB3]DPDPE turned out to be a more potent δ agonist than [l-DFAB3]DPDPE. Furthermore, [d-DFAB3]DPDPE showed over 100-fold higher δ agonist potency than [d-Abu3]DPDPE (Abu=2-aminobutyric acid), indicating that the fluorine substituents interact favorably with a δ opioid receptor subsite. © 1998 European Peptide Society and John Wiley & Sons, Ltd.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
