Opioid activity of 4-imidazolidinone positional analogues of Leu-Enkephalin.
Modulation of opioid activity was accomplished for analogues of Leu-enkephalin through incorporation of a 4-imidazolidinone moiety. The peptide backbone was constrained via a methylene bridge between two neighboring amides within its regular peptide sequence, which was expected to disrupt the secondary structure of the original molecule. Five positional analogues of Leu-enkephalin based on the same sequence and different location of the imidazolidinone-constrict were designed, synthesized, and examined for their affinity to micro-, delta- and kappa-opioid receptors.
Rinnová
Markéta
M
Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
Nefzi
Adel
A
Houghten
Richard A
RA
D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D007093:Imidazoles; D007202:Indicators and Reagents; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004743:Enkephalin, Leucine