新月形超分子四肽纳米结构
2020-11-20

John B. Matson研究团队对新月牙形超分子四肽纳米结构进行了研究。 该研究成果于2020年11月13日发表在国际知名学术期刊《美国化学会杂志》。

两亲性肽基构建基块的自组装产生了大量有趣的纳米结构,如带状、纤维和管。然而,利用肽自组装直接制备这些高度对称基序更低对称性的纳米结构仍然是一个巨大的挑战。

该研究发现,直径为28±3 nm的连续和规则新月形纳米结构是由一系列具有AdKSKSEX一般结构的四肽(Ad=金刚烷基,KS=拥有S-芳酰基硫肟(SATO)基团的赖氨酸残基官能化,E=谷氨酸残基,X=可变氨基酸残基)形成的。在半胱氨酸存在的情况下,新月形纳米结构的SATO单元释放出生物信号气体硫化氢(H2S),称为肽-H2S供体结合物共轭物(PHDC),其降低巨噬细胞中活性氧(ROS)的水平。

另外的体外研究表明,新月形纳米结构比普通的H2S供体和类似化学结构的PHDC(adkse)能更有效地减轻phorbol 12-肉豆蔻酸-13-醋酸酯诱导的细胞毒性,后者形成短纳米蠕虫而不是纳米新月体。细胞内化研究表明,纳米新月形PHDCs在降低巨噬细胞中ROS水平方面更为有效,因为它们比纳米蠕虫更好地进入细胞并留在细胞内,这突出了纳米结构形态如何影响药物传递的生物活性。

附:英文原文

Title: Crescent-Shaped Supramolecular Tetrapeptide Nanostructures

Author: Yin Wang, Zhao Li, Yulia Shmidov, Ryan J. Carrazzone, Ronit Bitton, John B. Matson

Issue&Volume: November 13, 2020

Abstract: Self-assembly of amphiphilic peptide-based building blocks gives rise to a plethora of interesting nanostructures such as ribbons, fibers, and tubes. However, it remains a great challenge to employ peptide self-assembly to directly produce nanostructures with lower symmetry than these highly symmetric motifs. We report here our discovery that persistent and regular crescent nanostructures with a diameter of 28 ± 3 nm formed from a series of tetrapeptides with the general structure AdKSKSEX (Ad = adamantyl group, KS = lysine residue functionalized with an S-aroylthiooxime (SATO) group, E = glutamic acid residue, and X = variable amino acid residue). In the presence of cysteine, the biological signaling gas hydrogen sulfide (H2S) was released from the SATO units of the crescent nanostructures, termed peptide–H2S donor conjugates (PHDCs), reducing levels of reactive oxygen species (ROS) in macrophage cells. Additional in vitro studies showed that the crescent nanostructures alleviated cytotoxicity induced by phorbol 12-myristate-13-acetate more effectively than common H2S donors and a PHDC of a similar chemical structure, AdKSKSE, that formed short nanoworms instead of nanocrescents. Cell internalization studies indicated that nanocrescent-forming PHDCs were more effective in reducing ROS levels in macrophages because they entered into and remained in cells better than nanoworms, highlighting how nanostructure morphology can affect bioactivity in drug delivery.

DOI: 10.1021/jacs.0c09399

Source: https://pubs.acs.org/doi/10.1021/jacs.0c09399

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