title: 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.
abstract: 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), less than Glu-Leu-Gly-NH2 (3), Thz-Leu-Gly-NH2 (4), Pip-Leu-Gly-NH2 (5), Aze-Leu-Gly-NH2 (6), L-delta 3,4-Pro-Leu-Gly-NH2 (7), and D-delta 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 an essential requirement for this tripeptide's ability to modulate dopamine receptors.
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D002417:Cattle; D002421:Caudate Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D009281:Naphthalenes / Q000378:metabolism*; D011392:Proline / Q000502:physiology*; D011487:Protein Conformation; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000378:metabolism*
chemical_list: D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C011639:ADTN; D009075:MSH Release-Inhibiting Hormone; D011392:Proline