Short oligoalanine helical peptides for supramolecular nanopore assembly and protein cytosolic delivery,RSC Chemical Biology

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Short oligoalanine helical peptides for supramolecular nanopore assembly and protein cytosolic delivery
RSC Chemical Biology ( IF 4.2 ) Pub Date : 2020-12-8 , DOI: 10.1039/d0cb00103a
Marta Pazo ₁ , Giulia Salluce ₁ , Irene Lostalé-Seijo ₁ , Marisa Juanes ₁ , Francisco Gonzalez _{2,

3} , Rebeca Garcia-Fandiño ₁ , Javier Montenegro ₁

Affiliation

In this work we report a rational design strategy for the identification of new peptide prototypes for the non-disruptive supramolecular permeation of membranes and the transport of different macromolecular giant cargos. The approach targets a maximal enhancement of helicity in the presence of membranes with sequences bearing the minimal number of cationic and hydrophobic moieties. The here reported folding enhancement in membranes allowed the selective non-lytic translocation of different macromolecular cargos including giant proteins. The transport of different high molecular weight polymers and functional proteins was demonstrated in vesicles and in cells with excellent efficiency and optimal viability. As a proof of concept, functional monoclonal antibodies were transported for the first time into different cell lines and cornea tissues by exploiting the helical control of a short peptide sequence. This work introduces a rational design strategy that can be employed to minimize the number of charges and hydrophobic residues of short peptide carriers to achieve non-destructive transient membrane permeation and transport of different macromolecules.

中文翻译：

用于超分子纳米孔组装和蛋白质胞质递送的短寡丙氨酸螺旋肽

在这项工作中，我们报告了一种合理的设计策略，用于鉴定用于膜的非破坏性超分子渗透和不同大分子巨型货物的运输的新肽原型。该方法的目标是在膜存在的情况下最大程度地增强螺旋度，该膜具有最少数量的阳离子和疏水部分的序列。这里报道的膜折叠增强允许包括巨蛋白在内的不同大分子货物的选择性非裂解易位。在囊泡和细胞中证明了不同高分子量聚合物和功能性蛋白质的转运效率和最佳活力。作为概念证明，通过利用短肽序列的螺旋控制，功能性单克隆抗体首次被转运到不同的细胞系和角膜组织中。这项工作引入了一种合理的设计策略，可用于最大限度地减少短肽载体的电荷数量和疏水残基，以实现不同大分子的非破坏性瞬时膜渗透和转运。

更新日期：2020-12-09

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