Morphiceptin and β-casomorphin-5 analogues containing a reduced peptide bond: Selective μ-receptor agonists and a novel μ antagonist, H-Tyr-Proψ(CH2-NH)Phe-Pro-Gly-OH

In order to prevent enzymatic degradation of β‐casomorphin‐5 (1) and morphiceptin, reduced peptide bonds were incorporated at the 2–3 and 3–4 bonds, respectively. The analogues were synthesized by a combination of solid phase methodology and reductive alkylation of resin‐bound peptide amines with Boc‐amino acid aldehydes (Boc: tert‐butyloxycarbonyl) in the presence of NaBH3CN. During reversed phase high pressure liquid chromatography purification, peak shape distortions could be observed. Epimerization was excluded, based on gas chromatography/mass spectroscopy analysis, which indicated acceptable levels of racemization (