Synthesis and Dopamine Receptor Modulating Activity of Novel Peptidomimetics ofl-Prolyl-l-leucyl-glycinamide Featuring α,α-Disubstituted Amino Acids
Citations Over Time
Abstract
In the present study, L-prolyl-L-leucyl-glycinamide (1) peptidomimetics 3a-3d and 4a-4d were synthesized utilizing alpha, alpha-disubstituted amino acids. These analogues were designed to explore the conformational effects of constraints at the phi3 and psi3 torsion angles. Constrained conformations were verified by the use of X-ray crystallography and circular dichroism. The effects of Pro-Leu-Gly-NH2 analogues 3a-3d and 4a-4d on enhancing rotational behavior induced by apomorphine in the 6-hydroxydopamine-lesioned animal models of Parkinson's disease were studied. The ability of these peptidomimetics to increase the binding of agonist N-propylnorapomorphine (NPA) to the dopamine D2 receptor was also examined. Extended analogue Pro-Leu-Deg-NH2 was the most active compound of this series. It was 10 times more potent and almost 2 times more effective than 1 in increasing apomorphine-induced rotations (56 +/- 15% at 1.0 mg/kg ip) and in enhancing [3H]NPA specific binding (40%).
Related Papers
- → Stereoisomers of apomorphine differ in affinity and intrinsic activity at presynaptic dopamine receptors modulating [3H]dopamine and [3H]acetylcholine release in slices of cat caudate(1983)54 cited
- → Effect of cyclo(Leu-Gly) on the supersensitivity of dopamine receptors in spontaneously hypertensive rats(1983)14 cited
- → Time course of rat motility response to apomorphine: A simple model for studying preferential blockade of brain dopamine receptors mediating sedation(1983)52 cited
- → 3H-apomorphine interactions with dopamine receptors in calf brain(1978)43 cited
- → Apomorphine-like effect of an aminotetralin on the linguomandibular reflex of the cat(1975)3 cited