Plant-derived peptides rubiscolin-6, soymorphin-6 and their c-terminal amide derivatives: Pharmacokinetic properties and biological activity. (October 2020)

• Record Type: Journal Article
• Authors: Stefanucci, Azzurra; Dimmito, Marilisa Pia; Tenore, Giancarlo; Pieretti, Stefano; Minosi, Paola; Zengin, Gokhan; Sturaro, Chiara; Calò, Girolamo; Novellino, Ettore; Cichelli, Angelo; Mollica, Adriano
• Is Part Of: Journal of functional foods. Volume 73(2020)
• Publication Date: 2020-10
• Subjects: Opioid peptides -- Rubiscolin-6 -- Soymorphin-6 -- Antinociception -- Antioxidant activity; DOR δ-opioid receptor -- MOR μ-opioid receptor -- FT formalin test -- TF tail flick test -- BBB blood brain barrier -- s.c. subcutaneous -- i.c.v. intracerebroventricular -- SM soymorphin -- BCM β-casomorphin -- GPI guinea pig ileum -- MVD mouse vas deferens -- EM-1 endomorphin-1 -- EM-2 endomorphin-2 -- STZ streptozocine -- SPPS solid phase peptide synthesis -- TMS trimethylsilane -- TBTU 2-(1H-Benzotriazole-1-yl)-1, 1, 3, 3-tetramethylaminium tetrafluoroborate -- HOBt hydroxybenzotriazole -- DIPEA N-Ethyldiisopropylamine -- DMF dimethylformamide -- TIPS triisopropylsilane -- ACN acetonitrile -- TFA trifluoroacetic acid -- ADME absorption, distribution, metabolism, excretion; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2020.104154
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Rubiscolin-6 and Soymorphin-6 are two natural bioactive peptides from spinach and cereals. Four peptides were obtained in excellent overall yields and purity following Fmoc-SPPS strategy. Rubiscolin-6 C -amide exhibits significative antinociceptive effect in in vivo tests. Rubiscolin-6 shows the best in vitro intestinal bioavailability in CaCo2 cell monolayer. Abstract: The aim of this work is to investigate the pharmacokinetic properties, antinociceptive and antioxidant activities of rubiscolin-6, soymorphin-6 and their C -terminal amides; The four peptides were synthesized following Fmoc-SPPS strategy to give the final peptides in excellent overall yields and purity following analytical RP-HPLC analysis. None of them shows antioxidant activity and α-tyrosinase inhibition in vitro . All compounds are able to activate G-protein coupled receptor at the δ-opioid receptor (DOR) at 100 μM concentration however, rubiscolin-6-amide exhibits significative antinociceptive effect after i.c.v. administration in the tail flick test (TF) and s.c. administration in the formalin test (FT). Rubiscolin-6 shows the best in vitro intestinal bioavailability in CaCo2 cell monolayer and stability to the brush border exopeptidases in the apical compartment. In silico experiments show the interaction of rubiscolin-6 and rubiscolin-6 amide at the binding cavity of DOR compared with the crystallographic ligand TIPP-NH2 .