Biphalin analogs containing β3-homo-amino acids at the 4,4′ positions: Synthesis and opioid activity profiles

Synthesis, binding affinities and metabolic stability of dimeric dermorphin analogs modified withβ3-homo-amino acids

“…Biphalin analog modified with β 3 ‐ homo ‐Phe in position 4,4′ showed remarkable binding affinity, with K i δ = 0.72 and K i μ = 1.1 nM and an increased enzymatic stability in human plasma . The incorporation of β 3 ‐ homo ‐Phe(NO 2 ) in position 4,4′ increases μ ‐affinities and slightly decreases δ ‐affinities (IC 50 μ = 0.72 nM; IC 50 δ = 4.66 nM ). It confirms that homologation of residue connected with linker in dimeric opioid analogs is generally well tolerated and improves activity and selectivity.…”

“…Hybrid α / β peptides fold the backbone in a manner more similar to the natural α ‐peptides than full β ‐peptides, and this, together with their high intrinsic metabolic stability, makes them good candidates for drug design . Various β 3 ‐ homo ‐amino acids have been used in the design of several classes of ligands, including opioid peptides . Incorporation of β 3 ‐ homo‐ phenylalanin or its analogs at the 4,4' positions of biphalin resulted in good opioid receptor affinities and antinociceptive activity .…”

“…Various β 3 ‐ homo ‐amino acids have been used in the design of several classes of ligands, including opioid peptides . Incorporation of β 3 ‐ homo‐ phenylalanin or its analogs at the 4,4' positions of biphalin resulted in good opioid receptor affinities and antinociceptive activity .…”

In vitro and in vivo activity of cyclopeptide Dmt-c[ d -Lys-Phe-Asp]NH 2 , a mu opioid receptor agonist biased toward β-arrestin

“…administration [24], induced less physical dependence than morphine [25] and could penetrate the BBB [26]. Several linear analogs of biphalin with amino acid substitutions in positions 2,2′ and 4,4′ were also reported [27,28].…”

Dimeric Dermorphin Analogues Containing β3-Homo-Amino Acids: Synthesis, Binding Affinities and Metabolic Stability

“…Various β 3 -homo-amino acids have been used in the design of several classes of ligands, including opioid peptides [4]. The incorporation of β 3 -homo-phenylalanine or its analogues at the 4,4' positions of biphalin resulted in good opioid receptor affinities and antinociceptive activity [5].…”