氨基酸构型对多肽纳米纤维体内分布的影响
发布时间：2019-06-05 15:11
【摘要】：目的比较由L构型和D构型氨基酸自组装形成的纳米纤维在体内分布的差异,为不同构型氨基酸自组装纳米多肽的体内应用提供指导。方法固相合成法合成多肽Nap-GFFYGRGD(L-肽)和Nap-GDFDFDYGRGD(D-肽),利用核磁和质谱对多肽分子进行结构表征。多肽溶液通过煮沸、冷却、自组装形成纳米纤维(L-纤维和D-纤维),透射电镜观察纳米纤维的微观形貌。125I标记多肽分子后,由其自组装形成的纳米纤维通过尾静脉注射入小鼠体内,分别在1、3、6和12 h采血并处死小鼠,取心、肝、脾、肺、肾、胃、大肠、小肠、肌肉、脑等主要器官,用γ计数仪测量其放射性强度。结果 L-肽和D-肽均可自组装形成纳米纤维,纤维直径约为10～20 nm,且两者微观形貌无明显差异。两种纳米纤维在体内的分布差异有统计学意义。D-纤维在注射后1 h的血液浓度为(8.17±0.32)%ID/g,但较迅速地从血液中清除;L-纤维浓度为(5.96±0.30)%ID/g,在注射后6 h基本保持不变。D-纤维主要分布于肝中而L纤维主要分布在胃中。结论氨基酸构型(D/L)对多肽纳米纤维在体内的分布影响显著,在未来的医学应用中考虑氨基酸构型对体内分布的影响有可能更好地指导多肽纳米纤维的应用。
[Abstract]:Objective to compare the distribution of nanofibers formed by L configuration and D configuration amino acid self-assembly in vivo, and to provide guidance for the application of amino acid self-assembly nanopeptides with different configurations in vivo. Methods peptides Nap-GFFYGRGD (L-peptide) and Nap-GDFDFDYGRGD (D-peptide) were synthesized by solid phase synthesis. The structure of polypeptide molecules was characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). Nanofibers (L-fibers and D-fibers) were formed by boiling, cooling and self-assembly of polypeptide solution. The micromorphology of nanofibers was observed by transmission electron microscope. After 125i labeled polypeptide molecules, The nanofibers formed by self-assembly were injected into mice through tail vein. Blood samples were collected at 1 h, 3 h, 6 h and 12 h, respectively, and the mice were killed. The main organs such as heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine, muscle, brain and so on were taken. The radioactivity intensity was measured by gamma counter. Results both L-peptide and D-peptide could be self-assembled to form nanofibers, the diameter of the fibers was about 10 鈮，
本文编号：2493619
[Abstract]:Objective to compare the distribution of nanofibers formed by L configuration and D configuration amino acid self-assembly in vivo, and to provide guidance for the application of amino acid self-assembly nanopeptides with different configurations in vivo. Methods peptides Nap-GFFYGRGD (L-peptide) and Nap-GDFDFDYGRGD (D-peptide) were synthesized by solid phase synthesis. The structure of polypeptide molecules was characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). Nanofibers (L-fibers and D-fibers) were formed by boiling, cooling and self-assembly of polypeptide solution. The micromorphology of nanofibers was observed by transmission electron microscope. After 125i labeled polypeptide molecules, The nanofibers formed by self-assembly were injected into mice through tail vein. Blood samples were collected at 1 h, 3 h, 6 h and 12 h, respectively, and the mice were killed. The main organs such as heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine, muscle, brain and so on were taken. The radioactivity intensity was measured by gamma counter. Results both L-peptide and D-peptide could be self-assembled to form nanofibers, the diameter of the fibers was about 10 鈮，
本文编号：2493619
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