Synthesis, binding affinities and metabolic stability of dimeric dermorphin analogs modified with β3‐homo‐amino acids

In this study, proteinogenic amino acids residues of dimeric dermorphin pentapeptides were replaced by the corresponding β3‐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 β3‐homo‐Tyr in place of Tyr (Tyr‐d‐Ala‐Phe‐Gly‐β3‐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. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. In this paper, we describe the synthesis, binding affinity and enzymatic stability of analogs dimeric dermorphin pentapeptides containing β3‐homo‐amino acids. Our studies have shown that analogs containing β3‐homo‐amino acids exhibit various degree of affinity to μ and δ receptors. Analog I (Tyr‐d‐Ala‐Phe‐Gly‐Tyr‐NH‐)2 exhibited good stability to human serum, whilst analog IV (Tyr‐d‐Ala‐Phe‐Gly‐β3‐homo‐Tyr‐NH‐)2, containing β3‐homo‐tyrosine in position 5,5', was found to be extremely stable in human plasma.
Source: Journal of Peptide Science - Category: Biochemistry Authors: Tags: Research Article Source Type: research