Synthesis,binding affinities and metabolic stability of dimeric dermorphin analogs modified with β3‐homo‐amino acids |
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| Authors: | Oliwia Frączak Anika Lasota Dagmara Tymecka Piotr Kosson Adriana Muchowska Aleksandra Misicka Aleksandra Olma |
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| Affiliation: | 1. Institute of Organic Chemistry, Lodz University of Technology, Lodz, Poland;2. Faculty of Chemistry, University of Warsaw, Warsaw, Poland;3. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland |
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| Abstract: | 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. |
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| Keywords: | β 3‐homo‐amino acids hybrid α /β dimeric dermorphin pentapeptides opioid receptors binding affinity enzymatic stability in human plasma |
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