Direct Influence of C-Terminally Substituted Amino Acids in the Dmt−Tic Pharmacophore on δ-Opioid Receptor Selectivity and Antagonism

2004 ◽  
Vol 47 (16) ◽  
pp. 4066-4071 ◽  
Author(s):  
Gianfranco Balboni ◽  
Severo Salvadori ◽  
Remo Guerrini ◽  
Lucia Negri ◽  
Elisa Giannini ◽  
...  
Keyword(s):  
Amino Acids ◽  
Opioid Receptor ◽  
Direct Influence ◽  
Receptor Selectivity ◽  
Δ Opioid Receptor ◽  
Opioid Receptor Selectivity

scholarly journals Role of steric interactions in the delta opioid receptor selectivity of [d-Pen2, d-Pen5]enkephalin

2009 ◽  
Vol 32 (1) ◽  
pp. 1-8 ◽  
Author(s):  
HENRY I. MOSBERG ◽  
RONALD C. HAASETH ◽  
KONDAREDDIAR RAMALINGAM ◽  
ALFRED MANSOUR ◽  
HUDA AKIL ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Delta Opioid Receptor ◽  
Receptor Selectivity ◽  
Steric Interactions ◽  
Opioid Receptor Selectivity

scholarly journals β2-Homo-Amino Acid Scan of µ-Selective Opioid Tetrapeptide TAPP

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2461 ◽  
Author(s):  
Dagmara Tymecka ◽  
Piotr F. J. Lipiński ◽  
Piotr Kosson ◽  
Aleksandra Misicka
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Human Plasma ◽  
Opioid Receptor ◽  
Molecular Modelling ◽  
Parent Compound ◽  
Common Element ◽  
Ionic Interaction ◽  
Receptor Affinity ◽  
Δ Opioid Receptor

TAPP (H-Tyr-d-Ala-Phe-Phe-NH2) is a potent, µ-selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a β2-Homo-amino acid (β2hAA) scan of the TAPP sequence. To this aim, 10 novel analogues have been synthesized and evaluated for µ-opioid and δ-opioid receptor affinity as well as for stability in human plasma. The derivatives included compounds in which a (R)- or (S)-β2-Homo-Homologue replaced the amino acids in the TAPP sequence. The derivatives with (R)- or (S)-β2hPhe4 turned out to bind µOR with affinities equal to that of the parent. β2hAAs in position 1 and 3 resulted in rather large affinity decreases, but the change differed depending on the stereochemistry. β2-Homologation in the second position gave derivatives with very poor µOR binding. According to molecular modelling, the presented α/β-peptides adopt a variety of binding poses with their common element being an ionic interaction between a protonable amine of the first residue and Asp147. A feature required for high µOR affinity seems the ability to accommodate the ring in the fourth residue in a manner similar to that found for TAPP. Contrary to what might be expected, several compounds were significantly less stable in human plasma than the parent compound.

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