Combined chemical modified endomorphin-1 and method for preparing same

Abstract

The present invention is four analogs of endomorphin-1, [GMLPC]-FM-1, [GMLDC]-EM-1, [GMDPC]-EM-1 and [GMDDC]-EM-1, prepared through liquid phase synthesis and their preparation process. Serial pharmacological activity identifying measurements shows that these four analogs have enzymolysis stability in brain plasmalemma and blood serum of mouse obviously higher than their precursor, longer pain relieving time, and higher integral liposolubility. The present invention is significant for developing endomorphin-1 into clinical polypeptide analgesic.

Description

technical field The present invention relates to a new class of analogs [GMLPC]-EM-1, [GMLDC]-EM-1, [GMDPC]-EM-1 and [GMDDC] of endomorphin-1 (Endomorphin-1, EM-1) ]-EM-1 and its preparation method. Background technique Endomorphin 1 (Tyr-Pro-Trp-Phe-NH 2 , EM-1) and endomorphin 2 (Tyr-Pro-Phe-Phe-NH 2 , EM-2) are two endogenous opioid peptides that selectively agonize mu opioid receptors with high efficiency. Studies have found that endomorphins can participate in the regulation of many functions such as pain perception, cardiovascular, respiratory, gastrointestinal, exercise, behavior, endocrine and immunity through binding to G protein-coupled μ opioid receptors, but its main role is Potent analgesic activity, can produce analgesic effect comparable to that of morphine with less side effects, especially they also show obvious analgesic activity in animal models of neuralgia. Because EM-1 has better therapeutic properties than EM-2, such as the separation of rewarding ...

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Problems solved by technology

However, EM-1 also has disadvantages similar to other endogenous opioid peptides, such as short duration of analgesia, lack of oral activity, poor enzymatic stability, rapid degradation in blood and brain, and short half-life. The presence of the BBB also hinders their access to the CNS to exert their effects, thus limiting the use of endomorphins as therapeutic drugs

Although many endomorphin analogues have been synthesized so far, there are few analogues that can be injected into the CNS to produce analgesia

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