Stark H, Lössner B, Matthies H
Institut für Neurobiologie und Hirnforschung, Akademie der Wissenschaften der DDR, Magdeburg.
Biomed Biochim Acta. 1987;46(10):687-94.
Derivatives of opiate-like acting beta-casomorphin (beta-CM), (Tyr-Pro-Phe-Pro-Gly), were prepared by substitution of D-amino acids. The metabolism of these analogs was studied in brain and liver homogenates. Their half-lives and the metabolites resulting from their biological degradation were determined by means of the HPLC-technique. Resistance to biological degradation, which was considerably enhanced in some derivatives, was shown to depend on the position of the D-amino acids. The following substances proved to be particularly stable: D-Pro2-beta-CM, Des-Tyr-D-Pro2-beta-CM, Des-Tyr-D-Phe3-beta-CM. The resulting metabolites suggest that the activity of proline-specific peptidases is predominant in the catabolic process. The degradation pattern of beta-CM-pentapeptides produced by peptidases in the brain and liver is completely different from that of the enkephalin-pentapeptides, which are likewise protected by substitution of D-stereoisomers for certain L-amino acids. The different degradation kinetics of beta-CM-pentapeptides in neuronal and non-neuronal tissue homogenates (liver) reflect the variation in activity of certain peptidases. Considering the half-lives that we have estimated, we suggest which of the peptides tested has a high resistance against biological degradation in vivo.
通过D-氨基酸取代制备了类阿片样作用的β-酪蛋白吗啡（β-CM）（酪氨酸-脯氨酸-苯丙氨酸-脯氨酸-甘氨酸）的衍生物。在脑和肝匀浆中研究了这些类似物的代谢。通过高效液相色谱技术测定了它们的半衰期以及生物降解产生的代谢产物。在某些衍生物中显著增强的对生物降解的抗性被证明取决于D-氨基酸的位置。以下物质被证明特别稳定：D-脯氨酸2-β-CM、去酪氨酸-D-脯氨酸2-β-CM、去酪氨酸-D-苯丙氨酸3-β-CM。产生的代谢产物表明脯氨酸特异性肽酶的活性在分解代谢过程中占主导地位。脑和肝中的肽酶产生的β-CM五肽的降解模式与脑啡肽五肽的降解模式完全不同，脑啡肽五肽同样通过用D-立体异构体取代某些L-氨基酸来保护。β-CM五肽在神经元和非神经元组织匀浆（肝脏）中的不同降解动力学反映了某些肽酶活性的变化。考虑到我们估计的半衰期，我们提出了所测试的肽中哪些在体内对生物降解具有高抗性。
