γ-环肽纳米管的合成及自组装应用研究

发布时间：2018-03-03 16:16

本文选题：自组装　切入点：γ-环肽　出处：《西南科技大学》2017年硕士论文　论文类型：学位论文

【摘要】：自组装环肽纳米管由于具有特殊的结构、生物相容性以及性质可控性,因此,可以用于抗菌、生物传感器、光电材料、药物传递以及离子通道等方面。目前,国内外对α-环肽、β-环肽、δ-环肽、α,γ-交替的环肽和α,ε-交替的环肽自组装形成的纳米管的研究都已有报道,但是关于γ-环肽分子组装成纳米管的研究却报道较少。因此对γ-氨基酸组成的γ-多肽、γ-环肽及γ-环肽纳米管性质的研究在化学、生物学和医学等领域具有潜在的应用前景。因此,本文对γ-环肽的合成、组装、表征以及通道性质进行了研究,为γ-环肽的深入研究提供理论及实验依据,结论如下:1、从3-环己烯甲酸出发,通过碘内酯化、脱碘、钯催化叠氮开环、选择性叠氮还原、氨基保护、手性拆分及氢化还原得到光学纯3-氨基环己基甲酸(γ-Ach),接着以其为原料首次合成得到系列具有刚性结构、生物相容性TEG侧链修饰的γ-多肽,并通过缩合试剂法进行多肽片段的缩合得到γ-环四肽21及γ-环六肽24,经过1H NMR、13C NMR、HRMS和MALDI-TOF-MS验证其结构。2、对合成得到的目标分子γ-环四肽21和γ-环六肽24环肽进行变温变浓核磁、变浓紫外、红外等发现氢键和π-π作用驱动着环肽自组装,并且以β-折叠形式组装。3、通过原子力显微镜(AFM)和透射电镜(TEM)对γ-环四肽21和γ-环六肽24组装形成的组装体结构进行微观形貌的观察发现同样的条件下γ-环六肽24易于形成单一的纤维状结构;在乙腈/水体系中,随着水含量的增加,γ-环四肽21和γ-环六肽24组装体的形貌从固体堆积到比较粗的纤维再到膜结构,证实了极性溶剂的加入可以影响环肽组装体的形貌,起到一定的调控作用。4、通过γ-环四肽21和γ-环六肽24在水通道实验及离子(Cl-、H+、OH-)通道荧光实验中的数据发现γ-环四肽21仅可以进行OH-的跨膜运输,而γ-环六肽24则可以进行H2O及OH-的跨膜运输,二者都不能进行Cl-、H+与阳离子ACh+、Na+和K+的转运。
[Abstract]:Self-assembled cyclic peptide nanotubes can be used in antibacterial, biosensor, optoelectronic materials, drug delivery and ion channels because of their special structure, biocompatibility and controllability. The studies on 伪 -cyclic peptide, 尾 -cyclic peptide, 未 -cyclic peptide, 伪, 纬 -alternating cyclic peptide and 伪, 蔚 -alternating cyclic peptide self-assembled nanotubes have been reported at home and abroad. However, there are few reports on the assembly of 纬 -cyclic peptides into nanotubes. Therefore, the studies on the properties of 纬 -polypeptides, 纬 -cyclic peptides and 纬 -cyclic peptide nanotubes composed of 纬 -amino acids are in chemistry. Therefore, the synthesis, assembly, characterization and channel properties of 纬 -cyclic peptides are studied in this paper, which provides theoretical and experimental basis for the further study of 纬 -cyclic peptides. The conclusions are as follows: 1. Starting from 3-cyclohexene formic acid, through iodization, deiodization, palladium catalyzed azide ring opening, selective azide reduction, amino protection, The optical pure 3-aminocyclohexyl formic acid (纬 -Achum) was synthesized by chiral resolution and hydrogenation. A series of 纬 -polypeptides with rigid structure and biocompatibility TEG side chain modification were synthesized for the first time. 纬 -cyclic tetrapeptide 21 and 纬 -cyclohexapeptide 24 were obtained by condensation of polypeptide fragments by condensation reagent. The structures of 纬 -cyclic tetrapeptide 21 and 纬 -cyclic hexapeptide 24 were confirmed by 1H NMR-13C NMR-HRMS and MALDI-TOF-MS. The synthesized target molecules, 纬 -cyclic tetrapeptide 21 and 纬 -cyclic hexapeptide 24 cyclic peptide, were densified by nuclear magnetic field at different temperature. It was found that hydrogen bond and 蟺-蟺 interaction drive cyclic peptide self-assembly. The composition of 纬 -cyclic tetrapeptide 21 and 纬 -cyclohexapeptide 24 was observed by atomic force microscope (AFM) and transmission electron microscopy (TEM). It is easy to form a single fibrous structure; In acetonitrile / water system, with the increase of water content, the morphology of 纬 -cyclic tetrapeptide 21 and 纬 -cyclic hexapeptide 24 assembled from solid to coarse fiber to membrane structure was confirmed. It was proved that the addition of polar solvent could affect the morphology of cyclic peptide assembly. Through the data of 纬 -cyclic tetrapeptide 21 and 纬 -cyclohexapeptide 24 in the water channel experiment and the fluorescence experiment in the ion channel, it was found that 纬 -cyclic tetrapeptide 21 could only transmembrane transport OH-. On the other hand, 纬 -cyclohexapeptide 24 can transport H _ 2O and OH- across the membrane, and neither of them can transport Cl-H with cationic ACh Na and K.
【学位授予单位】：西南科技大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1;O629.72

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