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

• 作者: Friederike M. Mansfeld Istvan Toth
• 来源期刊: 有机化学国际期刊(英文)
• 学科: 化学
• 关键词: ENDOMORPHIN-1 OPIOID Peptide CYCLISATION DISULFIDE
• 年，卷（期）: 2012,（1）
• 页码范围: 1-6
• 页数: 6页
• 分类号: O6

摘要

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.