64963-01-5Relevant articles and documents
Synthesis and antinociceptive activity of [D-Ala2]Leu-enkephalin derivatives conjugated with the adamantane moiety
Kitagawa, Kouki,Mizobuchi, Noriko,Hama, Teruo,Hibi, Tohru,Konishi, Ryoji,Futaki, Shiroh
, p. 1782 - 1787 (2007/10/03)
Based on the physicochemical and pharmacological properties of drugs having an adamantane skeleton, an adamantane-based moiety was evaluated as a drug carrier for poorly absorbed compounds, including peptides, active towards the central nervous system (CNS). Seven [D-Ala2]Leu-enkephalin derivatives conjugated with an adamantane-based moiety at the C-terminus or N-terminus were prepared by the solution-phase method and their biological activities were examined. The compounds derivatized at the C-terminus through an ester or amide linkage were much more lipophilic than the parent peptide and exhibited moderate in vitro opioid activity (guinea-pig ileum assay). Among them, four derivatives (1, 2, 4, 5), exhibited significant antinociceptive effects in an in vivo assay (mouse tail-pressure test) after subcutaneous administration. This result suggests that the introduction of the lipophilic adamantane moiety into [D-Ala2]Leu- enkephalin would improve the permeation of the poorly absorbed parent peptide through the blood-brain-barrier (BBB) without loss of antinociceptive effect.
A photoaffinity reagent to label the opiate receptors of guinea pig ileum and mouse vas deferens
Fujioka,Matsunaga,Nakayama,Kanaoka,Hayashi,Kangawa,Matsuo
, p. 836 - 840 (2007/10/02)
An enkephalin derivative, [D-Ala2,Leu5]enkephalin N-[(2-nitro-4-azidophenyl)amino]ethylamide, has been synthesized as a photoaffinity label for the opiate receptor. This compound retains the full biological activity of [D-Ala2,Leu5]enkephalin in guinea pig ileum and mouse vas deferens tests with IC50 values of 4.4 and 2.6 nM, respectively, and inhibits the binding of [3H]naloxone to rat brain membrane preparation with an IC50 value of 2.5 nM. Photolysis of a muscle strip of the guinea pig ileum or of the mouse vas deferens in the presence of the peptide derivative caused irreversible inhibition of electrically stimulated contractions with high efficiencies (80 and 66%, respectively), while the inhibitory effect in the dark was fully reversed by washing. This irreversible inhibition during photolysis was completely prevented by the presence of [D-Ala2,Leu5]enkephalin. These results demonstrate that {D-Ala2,Leu5]-enkephalin N-[(2-nitro-4-azidophenyl)amino]ethylamide is a prominent candidate as a photoaffinity label for the opiate receptor.