Modifications of the 4,4′-residues and sar studies of biphalin, a highly potent opioid receptor active peptide

• Published in: Bioorganic & medicinal chemistry letters Vol. 8; no. 5; pp. 555 - 560
• Main Authors: Li, Guigen, Haq, W., Xiang, Li, Lou, Bih-Show, Hughes, Robert, De Leon, Irene A., Davis, Peg, Gillespie, Terrence J., Romanowski, Marek, Zhu, Xiaoyun, Misicka, Aleksandra, Lipkowski, Andrzej W., Porreca, Frank, Davis, Thomas P., Yamamura, Henry I., O'Brien, David F., Hruby, Victor J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 03.03.1998; Elsevier
• Subjects: Analgesics - chemistry; Analgesics - pharmacology; Animals; Biological and medical sciences; Enkephalins - chemistry; Enkephalins - pharmacology; Guinea Pigs; In Vitro Techniques; Lipid Bilayers; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Receptors, Opioid, mu - drug effects; Structure-Activity Relationship; Thermodynamics; Rodentia; μ Opioid receptor; Smooth muscle; Liquid phase; Ileum; In vitro; Opioid peptide; Vas deferens; Chemical coupling; Vertebrata; Biological fixation; Mammalia; Guinea pig; Structure activity relation; Mouse; Tetrapeptide; Animal; Cross reaction; Dimer; Peptide synthesis; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(98)00065-1

Modifications of 4,4′ residues of Biphalin have resulted in greater binding selectivity and biological potency for the μ opioid receptor. A higher partition coefficient across the phospholipid bilayer membrane has been achieved by using a β-branched unusual amino acids. Biphalin, a highly potent antinociceptive peptide, has been modified on 4, 4′ positions by using β-branched and aromatic substituted unusual amino acids. For example: (Tyr-D-Ala-Gly-Phe-NH) 2 ---> (Tyr-D-Ala-Gly-(2S,3R)β-Me-Phe-NH) 2