Synthesis, binding affinities and metabolic stability of dimeric dermorphin analogs modified with β3-homo-amino acids
Oliwia Frączak1, Anika Lasota1, Dagmara Tymecka2
1Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
Abstract:
In this study, proteinogenic amino acids residues of dimeric dermorphin pentapeptides were replaced by the corresponding β(3)-homo-amino acids. The potency and selectivity of hybrid α/β dimeric dermorphin pentapeptides were evaluated by competetive receptor binding assay in the rat brain using [3H]DAMGO (a μ ligand) and [3H]DELT (a δ ligand). Tha analog containing β(3)-homo-Tyr in place of Tyr (Tyr-D-Ala-Phe-Gly-β(3)-homo-Tyr-NH-)2 showed good μ receptor affinity and selectivity (IC50 = 0.302, IC50 ratio μ/δ = 68) and enzymatic stability in human plasma.
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