Novel glycosylated endomorphin-2 analog produces potent centrally-mediated antinociception in mice after peripheral administration.
Bioorg Med Chem Lett
; 23(24): 6673-6, 2013 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-24220171
ABSTRACT
We report the synthesis and pharmacological characterization of a novel glycosylated analog of a potent and selective endogenous µ-opioid receptor (MOP) agonist, endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2), obtained by the introduction in position 3 of the tyrosine residue possessing the glucose moiety attached to the phenolic function via a ß-glycosidic bond. The improved blood-brain barrier permeability and enhanced antinociceptive effect of the novel glycosylated analog suggest that it may be a promising template for design of potent analgesics. Furthermore, the described methodology may be useful for increasing the bioavailability and delivery of opioid peptides to the CNS.
Palabras clave
1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate; 2-chloro-4,6-bis[3-(perfluorohexyl)propyloxy]-1,3,5-triazine; AgOTf; Antinociception; BBB; CDMT; CNS; DMF; EM-2; Endomorphin-2; Fmoc; GPI assay; HATU; HR-ESI-MS; MOP; N-(9-fluorenylmethyloxycarbonyl); NALME; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; Peripheral administration; RP HPLC; TBTU; TFA; bloodbrain barrier; central nervous system; dimethylformamide; endomorphin-2; guinea pig ileum assay; high-resolution electrospray ionization mass spectrometry; intravenous; iv; naloxone methiodide; reversed-phase high-performance liquid chromatography; silver triflate; trifluoroacetic acid; µ-opioid receptor; µ-opioid receptor (MOP)
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Receptores Opioides mu
/
Analgésicos
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2013
Tipo del documento:
Article