【摘要】：目的比較由L構(gòu)型和D構(gòu)型氨基酸自組裝形成的納米纖維在體內(nèi)分布的差異,為不同構(gòu)型氨基酸自組裝納米多肽的體內(nèi)應(yīng)用提供指導(dǎo)。方法固相合成法合成多肽Nap-GFFYGRGD(L-肽)和Nap-GDFDFDYGRGD(D-肽),利用核磁和質(zhì)譜對(duì)多肽分子進(jìn)行結(jié)構(gòu)表征。多肽溶液通過煮沸、冷卻、自組裝形成納米纖維(L-纖維和D-纖維),透射電鏡觀察納米纖維的微觀形貌。125I標(biāo)記多肽分子后,由其自組裝形成的納米纖維通過尾靜脈注射入小鼠體內(nèi),分別在1、3、6和12 h采血并處死小鼠,取心、肝、脾、肺、腎、胃、大腸、小腸、肌肉、腦等主要器官,用γ計(jì)數(shù)儀測量其放射性強(qiáng)度。結(jié)果 L-肽和D-肽均可自組裝形成納米纖維,纖維直徑約為10～20 nm,且兩者微觀形貌無明顯差異。兩種納米纖維在體內(nèi)的分布差異有統(tǒng)計(jì)學(xué)意義。D-纖維在注射后1 h的血液濃度為(8.17±0.32)%ID/g,但較迅速地從血液中清除;L-纖維濃度為(5.96±0.30)%ID/g,在注射后6 h基本保持不變。D-纖維主要分布于肝中而L纖維主要分布在胃中。結(jié)論氨基酸構(gòu)型(D/L)對(duì)多肽納米纖維在體內(nèi)的分布影響顯著,在未來的醫(yī)學(xué)應(yīng)用中考慮氨基酸構(gòu)型對(duì)體內(nèi)分布的影響有可能更好地指導(dǎo)多肽納米纖維的應(yīng)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，

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