A. Misicka et al., STRUCTURE-ACTIVITY RELATIONSHIP OF BIPHALIN - THE SYNTHESIS AND BIOLOGICAL-ACTIVITIES OF NEW ANALOGS WITH MODIFICATIONS IN POSITION-3 AND POSITION-4, Life sciences, 60(15), 1997, pp. 1263-1269
Citations number
16
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
New analogues of biphalin [(Tyr-D-Ala-Gly-Phe-NH-)(2)] with modificati
ons of amino acid residues in positions 3,3' and 4,4' have been synthe
sized. The potency and selectivity of these analogues were evaluated b
y competitive radioreceptor binding assay in the rat brain using [H-3]
CTOP (mu ligand) and [H-3][p-Cl-Phe(4)]DPDPE (delta ligand) as ligands
, and by bioassay in the mouse vas deferens (MVD, delta receptor assay
) and guinea pig ileum (GPI, mu receptor assay). The symmetrical subst
itution of phenylalanine in positions 4 and 4' with p-fluorophenylalan
ine or p-nitrophenylalanine resulted in an enhancement of the affinity
at both delta and mu receptors, with some increase of the selectivity
for delta opioid receptors. The analogue containing p-chlorophenylala
nine in positions 4 and 4' is the most selective to the delta receptor
s in this series, with a selectivity ratio about 5. The symmetrical su
bstitution of the glycine-3 residue with phenylalanine resulted in a d
ecrease of binding affinities and biological potencies at both mu & de
lta receptors.