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氨基酸构型对多肽纳米纤维体内分布的影响
  • ISSN号:0253-9896
  • 期刊名称:天津医药
  • 时间:0
  • 页码:-
  • 分类:R318.08[医药卫生—生物医学工程;医药卫生—基础医学]
  • 作者机构:北京协和医学院&, 中国医学科学院放射医学研究所,天津市放射医学与分子核医学重点实验室,300192
  • 相关基金:国家自然科学基金资助项目(项目编号:51203189,51303213);天津市自然科学基金资助项目(项目编号:13JCZDJC28100);协和青年基金和中央高校基本科研业务费专项资金(项目编号:3332013045);放射医学研究所学科发展基金资助项目(项目编号:SF1314)
  • 相关项目:胶束表面亲疏水性与其体内分布关系的研究
中文摘要:

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。

英文摘要:

Objective To compare the biodistribution difference of peptide nanofibers, which were self-assembled by peptide composed of L-or D-amino acids, respectively, and provide the guidance for the in vivo applications of peptide nanofibers. Methods The Nap-GFFYGRGD (L-peptide) and Nap-GDFDFDYGRGD (D-peptide, F and Y were D-configura-tion) were synthesized with solid phase peptide synthesis (SPPS). The structure of the two peptides was identified by nuclear magnetic resonance spectroscopy (1H NMR) and high-resolution mass spectrometry (HR-MS). The two peptides could self-assemble into nanofibers during the cooling process after being boiled. The morphology of the nanofibers was observed with transmission electron microscope (TEM). The peptides were radiolabeled with iodine-125 and self-assembled into nanofi-bers, which were then administered into BALB/c mice via tail vein. The blood samples were collected and then mice were sacrificed at 1, 3, 6 and 12 hours. The main organs (heart, liver, spleen, lung, kidney, stomach, large intestine, small intes-tine, muscle and brain) were isolated and weighed. The radioactivity of organs was detected with a gamma counter. Results The two peptides could self-assemble into nanofibers with diameter of 10-20 nanometers. There were no significant differ-ences in the diameter and morphology between two naofibers. There was significant difference in the biodistribution between two nanofibers. The blood concentration of D-fiber was (8.17±0.32)%ID/g at one hour after injection and then cleared rapid-ly from the blood. The blood concentration of L-fiber was (5.96±0.30)%ID/g at one hour after injection and maintained at a stable level for six hours. The L-fiber was mainly distributed in stomach while the D-fiber was mainly accumulated in liver. Conclusion The configuration of amino acids (D/L) could affect the biodistribution of peptide nanofibers dramatically, which may provide the guidance for the medical applications of peptide nanofibe

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期刊信息
  • 《天津医药》
  • 中国科技核心期刊
  • 主管单位:天津市卫生和计划生育委员会
  • 主办单位:天津市医学科学技术信息研究所
  • 主编:王贺胜
  • 地址:天津市和平区贵州路96号D座
  • 邮编:300070
  • 邮箱:tjyybjb@sina.com
  • 电话:022-23337519
  • 国际标准刊号:ISSN:0253-9896
  • 国内统一刊号:ISSN:12-1116/R
  • 邮发代号:6-3
  • 获奖情况:
  • 两年荣获天津市一级期刊、优秀期刊奖,首届、第四、五、六届华北地区优秀期刊奖,第二、三届华北地区十佳期刊奖,第一、二届北方优秀期刊奖,国家科技期刊方阵双百期刊,全国优秀期刊奖
  • 国内外数据库收录:
  • 俄罗斯文摘杂志,美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2000版)
  • 被引量:21279