Synthesis of Pro-Leu-Gly-NH₂Analogues Modified at the Prolyl Residue and Evaluation of Their Effects on the Receptor Binding Activity of the Central Dopamine Receptor Agonist, ADTN

Several analogues of L-prolyl-L-leucylglycinamide (PLG) were synthesized wherein the prolyl residue was replaced with other heterocyclic amino acid residues. Among the analogues synthesized were D-Pro-Leu-Gly-NH₂(2), <Glu-Leu-Gly-NH₂(3), Thz-Leu-Gly-NH₂(4), Pip-Leu-Gly-NH₂(5), Aze-Leu-Gly-NH₂(6), L-Δ³⁴-Pro-Leu-Gly-NH₂(7), and D-Δ^3,4-Pro-Leu-Gly-NH₂(8). These analogues were tested for their ability to enhance the binding of the agonist 2-amino-6,7-dihydroxy-l,2,3,4-tetrahydronaphthalene to central dopamine receptors. Analogues 2, 3, and 5–7 showed activity comparable to that of PLG, while the tripeptides 4 and 8 were found to be inactive. The results show that the N-terminal prolyl residue of PLG is not an essential requirement for this tripeptide's ability to modulate dopamine receptors.