Synthesis of Pro-Leu-Gly-NH2 Analogues Modified at the Prolyl Residue and Evaluation of Their Effects on the Receptor Binding Activity of the Central Dopamine Receptor Agonist, ADTN

Article abstract of DOI:10.1021/jm00160a052

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), 3,4-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-1,2,3,4-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 essential requirement for this tripeptide's ability to modulate dopamine receptors.