title: Analogues of deltorphin I containing conformationally restricted amino acids in position 2: structure and opioid activity.
abstract: New analogues of deltorphin I (DT I, Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2 ), with the D-Ala residue in position 2 replaced by α-methyl-β-azido(amino, 1-pyrrolidinyl, 1-piperidinyl or 4-morpholinyl)alanine, were synthesized by a combination of solid-phase and solution methods. All ten new analogues were tested for receptor affinity and selectivity to μ- and δ-opioid receptors. The affinity of analogues containing (R) or (S)-α-methyl-β-azidoalanine in position 2 to δ-receptors strongly depended on the chirality of the α,α-disubstituted residue. Peptide II, containing (S)-α-methyl-β-azidoalanine in position 2, displayed excellent δ-receptor selectivity with its δ-receptor affinity being only three times lower than that of DT I.
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.forename: Oliwia
authors.initials: O
authors.lastname: Frączak
authors.forename: Anna
authors.initials: A
authors.lastname: Leśniak
authors.forename: Adriana
authors.initials: A
authors.lastname: Muchowska
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
authors.forename: Michał
authors.initials: M
authors.lastname: Nowakowski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Ejchart
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Olma
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D008024:Ligands; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C060208:deltorphin I, Ala(2)-
keywords: deltorphin I analogues; opioid activities; opioid peptides; α,α-disubstituted glycines