title: Synthesis, binding affinities and metabolic stability of dimeric dermorphin analogs modified with β3-homo-amino acids.
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.
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
authors.forename: Oliwia
authors.initials: O
authors.lastname: Frączak
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
authors.forename: Anika
authors.initials: A
authors.lastname: Lasota
authors.affiliation: Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093, Warsaw, Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Tymecka
authors.affiliation: Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 01-793, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kosson
authors.affiliation: Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 01-793, Warsaw, Poland.
authors.forename: Adriana
authors.initials: A
authors.lastname: Muchowska
authors.affiliation: Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093, Warsaw, Poland.|Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 01-793, Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Misicka
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Olma
mesh_terms: D000613:Aminobutyrates / Q000737:chemistry*; D000818:Animals; D001667:Binding, Competitive; D004355:Drug Stability; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D018847:Opioid Peptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D000613:Aminobutyrates; D018847:Opioid Peptides; D011957:Receptors, Opioid; C030058:dermorphin; D014443:Tyrosine; C014328:2-amino-4-phenylbutyric acid
keywords: enzymatic stability in human plasma; hybrid α/β dimeric dermorphin pentapeptides; opioid receptors binding affinity; β3-homo-amino acids