Synthesis and Dopamine Receptor Modulating Activity of Novel Peptidomimetics ofl-Prolyl-l-leucyl-glycinamide Featuring α,α-Disubstituted Amino Acids Journal Articles uri icon

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  • 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%).


  • Evans, Margaret C
  • Pradhan, Ashish
  • Venkatraman, Shankar
  • Ojala, William H
  • Gleason, William B
  • Mishra, Ram
  • Johnson, Rodney L

publication date

  • April 22, 1999