Alkylated RALA-Derived Peptides for Efficient Gene Delivery.

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2024-11-13 DOI:10.1021/acs.biomac.4c01355

Xuelin Zhang, Yexi Zhang, Xi Rong, Chuanmei Tang, Huiye Liu, Lei Yue, Rongxin Su, Yuefei Wang, Wei Qi

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Abstract

RALA is an amphipathic cationic peptide demonstrated to be a low-toxicity and high-efficiency delivery platform for the systemic delivery of nucleic acid therapeutics. This work reports three RALA-derived peptides modified with N-terminal palmitic acid, engineered through amino acid substitutions and truncated sequences. All three peptides have good nucleic acid encapsulation, release and uptake, biocompatibility, and endolysosome escape. The siRNA transfection efficiency is about 90%, and the silencing rate of GA (C16-GLFWHHHARLARALARHLARALRA) exceeds that of lipofectamine 2000 (siRNA concentration = 50 nM). Truncating the peptide chain while retaining a certain amount of arginine ensures an effective particle size. Replacing glutamic acid with three histidines ensures an effective zeta potential and accelerates the endosome escape process through the proton sponge phenomenon. Introducing phenylalanine enhances the carrier-cell interaction. We believe that they are powerful carriers of siRNA therapy and may have good application prospects in treating various diseases.

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用于高效基因传递的烷基化 RALA 衍生肽。

RALA 是一种两性阳离子肽，已被证明是一种低毒、高效的核酸治疗药物全身给药平台。这项研究报告了通过氨基酸置换和截短序列改造的三种 N 端棕榈酸修饰的 RALA 衍生肽。这三种肽都具有良好的核酸封装、释放和吸收能力、生物相容性和溶酶体内逃逸能力。siRNA 的转染效率约为 90%，GA（C16-GLFWHHHARLARALARHLARALRA）的沉默率超过了 lipofectamine 2000（siRNA 浓度 = 50 nM）。截断肽链并保留一定量的精氨酸可确保有效的粒径。用三个组氨酸取代谷氨酸可确保有效的 zeta 电位，并通过质子海绵现象加速内质体逸出过程。苯丙氨酸的引入增强了载体与细胞之间的相互作用。我们相信，它们是 siRNA 治疗的强大载体，在治疗各种疾病方面具有良好的应用前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.