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Membrane Internalization Mechanisms and Design Strategies of Arginine-Rich Cell-Penetrating Peptides

Journal

Publisher

MDPI
DOI: 10.3390/ijms23169038

Keywords

CPPs; arginine-rich peptide; non-covalent interaction; mechanism of internalization; peptide design; biomedical applications

Funding

  1. Industry of Shandong Province [2020KJC-CG04]
  2. Mitacs Fellowship (Canada) [IT18262]

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Cell-penetrating peptides (CPPs) have the ability to deliver chemical drugs, nucleic acids, and macromolecules into cells, and understanding their membrane internalization mechanisms and design strategies is of great importance. Arginine-rich peptides, with their unique cell penetration properties, have attracted significant attention. The penetration ability of arginine-rich peptides is related to the number of arginine residues, arginine optical isomers, primary sequence, secondary and ternary structures, etc. Applications of arginine-rich peptides include drug/RNA delivery systems, biosensors, and blood-brain barrier penetration, among others.
Cell-penetrating peptides (CPPs) have been discovered to deliver chemical drugs, nucleic acids, and macromolecules to permeate cell membranes, creating a novel route for exogenous substances to enter cells. Up until now, various sequence structures and fundamental action mechanisms of CPPs have been established. Among them, arginine-rich peptides with unique cell penetration properties have attracted substantial scientific attention. Due to the positively charged essential amino acids of the arginine-rich peptides, they can interact with negatively charged drug molecules and cell membranes through non-covalent interaction, including electrostatic interactions. Significantly, the sequence design and the penetrating mechanisms are critical. In this brief synopsis, we summarize the transmembrane processes and mechanisms of arginine-rich peptides; and outline the relationship between the function of arginine-rich peptides and the number of arginine residues, arginine optical isomers, primary sequence, secondary and ternary structures, etc. Taking advantage of the penetration ability, biomedical applications of arginine-rich peptides have been refreshed, including drug/RNA delivery systems, biosensors, and blood-brain barrier (BBB) penetration. Understanding the membrane internalization mechanisms and design strategies of CPPs will expand their potential applications in clinical trials.

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