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Degradation of thymic humoral factor γ2 in human, rat and mouse blood: An experimental and theoretical study.
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics ( IF 3.2 ) Pub Date : 2020-06-05 , DOI: 10.1016/j.bbapap.2020.140467
Marcella Martignoni 1 , Margherita Benedetti 2 , Gavin P Davey 1 , Keith F Tipton 1 , Andrew G McDonald 1
Affiliation  

The degradation of the immunomodulatory octapeptide, thymic humoral factor γ2 (THF-γ2, thymoctonan) has been studied in whole blood samples from human, rat and mouse. The peptide, Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu, was shown to be rapidly degraded by peptidases. The half-life of the intact peptide was less than 6 min at 37 °C in blood from the three species tested. The main fragments formed from THF-γ2 were found to be Glu-Asp-Gly-Pro-Lys-Phe-Leu (2–8), Asp-Gly-Pro-Lys-Phe-Leu (3–8) and Glu-Asp-Gly-Pro-Lys (2–6) in human and in rat blood and 2–8 and 2–6 in mouse blood. Analysis of the time course of degradation revealed a sequential removal of single amino acids from the N-terminus (aminopeptidase activities) in a process that was apparently unable to cleave the Gly-Pro bond (positions 4–5 in the peptide) together with an independent cleavage of the Lys-Phe bond (positions 6–7 in the peptide) to release the dipeptide Phe-Leu. This behaviour and the effects of inhibitors showed the involvement of metallo-exopeptidases in the N-terminal digestion and a phosphoramidon-sensitive metallo-endopeptidase in the cleavage of the Lys-Phe bond. The degradation patterns in human blood were modelled in terms of the competing pathways involved approximating to first-order kinetics, and an analytical solution obtained via the method of Laplace Transforms. The half-life of THF degradation in whole rat blood sample was found to be significantly lower than in human or mouse.



中文翻译:

胸腺体液因子γ2在人,大鼠和小鼠血液中的降解:一项实验和理论研究。

免疫调节八肽的降解,胸腺体液因子γ 2(THF- γ 2,thymoctonan)已经从人,大鼠和小鼠的全血样品中进行了研究。肽,Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu,被肽酶迅速降解。在测试的三种物种的血液中,完整肽的半衰期在37°C下不到6分钟。由THF- γ形成的主要片段发现2个是Glu-Asp-Gly-Pro-Lys-Phe-Leu(2-8),Asp-Gly-Pro-Lys-Phe-Leu(3-8)和Glu-Asp-Gly-Pro-Lys (2–6)在人和大鼠的血液中,以及2–8和2–6在小鼠的血液中。对降解时间过程的分析显示,在N端顺序去除单个氨基酸(氨肽酶活性)的过程中,该过程显然无法裂解Gly-Pro键(肽中的4-5位)以及一个氨基酸。独立裂解Lys-Phe键(肽中的6-7位)以释放二肽Phe-Leu。这种行为和抑制剂的作用表明,金属外肽酶参与N末端的消化,而磷酰胺敏感的金属内肽酶参与Lys-Phe键的切割。根据涉及到一级动力学的竞争途径以及通过拉普拉斯变换法获得的分析溶液,对人血中的降解模式进行了建模。发现全大鼠血样中THF降解的半衰期显着低于人或小鼠。

更新日期:2020-06-05
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