Synthesis and Plasma Stability of Disulfide-Bridged Cyclic Endomorphin-1 Derivatives

Friederike M. Mansfeld, Istvan Toth

School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Australia.

DOI: 10.4236/ijoc.2012.21001                

Abstract

Endomorphin-1 is an endogenous opioid peptide that mediates pain relief through interaction with the μ-opioid receptor in the central nervous system. To enhance the metabolic stability of this tetrapeptide, cyclisation through the formation of a disulfide bridge between the side chains of cysteine residues added to the sequence was explored. A further increase in stability was achieved through N-terminal modification with lipoamino acid and lactose succinamic acid, and the inclusion of D-amino acids. The latter also provided an alternative spatial arrangement of the aromatic side chains. The lipidated cyclic derivatives were insoluble in aqueous buffer, however, the cyclic peptides and glycopeptides showed greatly improved stability towards enzymatic degradation in human plasma.

Keywords

Endomorphin-1; Opioid Peptide; Cyclisation; Disulfide

Conflicts of Interest

The authors declare no conflicts of interest.

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