Synthesis of porcine leumorphin and some of its biological activities |
| |
Authors: | Yoshihito Yamamoto Chizuko Yanaihara Yumiko Katsumaru Tohru Mochizuki Akihiro Tobe Mitsuo Egawa Hiroo Imura Shosaku Numa Noboru Yanaihara |
| |
Institution: | 1. Laboratory of Cellular Metabolism, National Institute for Physiological Sciences, Okazaki, Japan;2. Laboratory of Bioorganic Chemistry, Shizuoka College of Pharmacy, Shizuoka, Japan;3. Biosciences Laboratory, Research Center, Mitsubishi Chemical Industries, Ltd., Yokohama, Japan;4. Faculty of Medicine, Kyoto University, Kyoto, Japan |
| |
Abstract: | The carboxy-terminal nonacosapeptide sequence of porcine preproenkephalin B contains the sequence of Leu-enkephalin at its amino terminus. The endogenous existence of this peptide, leumorphin, has not yet been proved. Synthesis of leumorphin was carried out by a solid-phase technique and the purity and structure of the synthetic peptide were confirmed. Synthetic porcine leumorphin exhibited a dose-dependent opiate effect (ED50 4.70 · 10?9 M) on electrically stimulated contraction of the guinea pig ileum preparation. The potency was about 100 times as high as that of Leu-enkephalin. Leumorphin was less potent than dynorphin(1–13) (ED50 0.38 · 10?9 M) but it was more active than (ED50 18 · 10?9 M). The opiate activity was only partially reversed by naloxone. Intracisternal injection of synthetic leumorphin caused significant analgesia in mice (ED50 7.31 nmol/mouse). The potency was lower than that of (ED50 0.60 nmol/mouse) but higher than that of dynorphin(1–13) (ED50 16.10 nmol/mouse). Intracisternally injected leumorphin did not produce such a violent behavioral effect as did dynorphin(1–13), and it exhibited a mild sedative effect. The data supports the concept that leumorphin is a new type of opioid peptide and that the synthetic preparation will be useful for further biological and immunological studies on this peptide. |
| |
Keywords: | leumorphin preproenkephalin B solid-phase peptide synthesis opiate activity analgesic activity |
本文献已被 ScienceDirect 等数据库收录! |
|