Pazo Marta, Salluce Giulia, Lostalé-Seijo Irene, Juanes Marisa, Gonzalez Francisco, Garcia-Fandiño Rebeca, Montenegro Javier
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela 15782 Santiago de Compostela Spain
Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela 15782 Santiago de Compostela Spain.
RSC Chem Biol. 2020 Dec 8;2(2):503-512. doi: 10.1039/d0cb00103a. eCollection 2021 Apr 1.
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.
在这项工作中，我们报告了一种合理的设计策略，用于鉴定新型肽原型，以实现膜的非破坏性超分子渗透以及不同大分子巨型货物的运输。该方法的目标是在存在带有最少阳离子和疏水部分序列的膜的情况下，最大程度地增强螺旋度。此处报道的膜中折叠增强允许不同大分子货物（包括巨型蛋白质）进行选择性非裂解转运。在囊泡和细胞中证明了不同高分子量聚合物和功能蛋白的运输具有出色的效率和最佳的活力。作为概念验证，通过利用短肽序列的螺旋控制，首次将功能性单克隆抗体运输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，可用于最小化短肽载体的电荷数和疏水残基数量，以实现不同大分子的非破坏性瞬时膜渗透和运输。
