Synthesis, binding affinities and metabolic stability of dimeric dermorphin analogs modified with β3‐homo‐amino acids. (April 2016)

• Record Type: Journal Article
• Authors: Frączak, Oliwia; Lasota, Anika; Tymecka, Dagmara; Kosson, Piotr; Muchowska, Adriana; Misicka, Aleksandra; Olma, Aleksandra
• Is Part Of: Journal of peptide science. Volume 22:Number 4(2016:Apr.)
• Page Start: 222
• Page End: 227
• Publication Date: 2016-04
• Subjects: β3‐homo‐amino acids -- hybrid α/β dimeric dermorphin pentapeptides -- opioid receptors binding affinity -- enzymatic stability in human plasma; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.2869
• Languages: English
• ISSNs: 1075-2617

Abstract

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. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Abstract : In this paper, we describe the synthesis, binding affinity and enzymatic stability of analogs dimeric dermorphin pentapeptides containing β 3 ‐ homo ‐amino acids. Our studies have shown that analogs containing β 3 ‐ homo ‐amino acids exhibit various degree of affinity to μ and δ receptors. AnalogI (Tyr‐d ‐Ala‐Phe‐Gly‐Tyr‐NH‐)2 exhibited good stability to human serum, whilst analogIV (Tyr‐d ‐Ala‐Phe‐Gly‐ β 3 ‐ homo ‐Tyr‐NH‐)2, containing β 3 ‐ homo ‐tyrosine in position 5, 5', was found to be extremely stable in human plasma.