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.4c0135510.1021/acs.biomac.4c01355

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

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引用次数: 0

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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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.