CAJ | 학술논문

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。
목적：비교유L구형화D구형안기산자조장형성적납미섬유재체내분포적차이，위불동구형안기산자조장납미다태적체내응용제공지도。방법고상합성법합성다태Nap-GFFYGRGD（L-태）화Nap-GDFDFDYGRGD （D-태），이용핵자화질보대다태분자진행결구표정。다태용액통과자비、냉각、자조장형성납미섬유（L-섬유화D-섬유），투사전경관찰납미섬유적미관형모。125I표기다태분자후，유기자조장형성적납미섬유통과미정맥주사입소서체내，분별재1、3、6화12 h채혈병처사소서，취심、간、비、폐、신、위、대장、소장、기육、뇌등주요기관，용γ계수의측량기방사성강도。결과 L-태화D-태균가자조장형성납미섬유，섬유직경약위10~20 nm，차량자미관형모무명현차이。량충납미섬유재체내적분포차이유통계학의의。D-섬유재주사후1 h적혈액농도위（8.17±0.32）%ID/g，단교신속지종혈액중청제；L-섬유농도위（5.96±0.30）%ID/g，재주사후6 h기본보지불변。D-섬유주요분포우간중이L섬유주요분포재위중。결론안기산구형（D/L）대다태납미섬유재체내적분포영향현저，재미래적의학응용중고필안기산구형대체내분포적영향유가능경호지지도다태납미섬유적응용。
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 nanofibers.