Cell-Penetrating Peptides

Zorko, Matjaž; Langel, Ülo

doi:10.1007/978-1-0716-1752-6_1

Cited by 21 publications

(19 citation statements)

References 167 publications

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“…previous studies 23 , it is reasonable to assume that endocytosis is the dominant mechanism of molecular transduction under our experimental conditions of electrotransfection. It is noted that the endocytotic mechanism was also reported in previous studies using a cell penetration peptide (CPP) 26 .…”

Section: Time-dependent Chemical Shift Changes Of In-cell Nmr Using E...supporting

confidence: 56%

Structure and Dynamics of a Protein Inside Endosomal Vesicles in Intact Human Cells

Kodama

Furuita

Sugiki

et al. 2022

Preprint

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With in-cell NMR, the structural and dynamic features of proteins can be analyzed directly in living cells at atomic resolution. However, in mammalian cells, such as human cells, the structural/dynamic features and physiological functions are not fully understood at atomic resolution. In this study, we developed a method for the highly viable and efficient introduction of stable isotope-labeled proteins into human cells by electrotransfection. Thus, it was possible to perform in-cell NMR to study the structural/dynamic features of intracellular proteins with a time resolution of a minute. The transfected proteins were localized in intracellular vesicles and gradually degraded as the vesicles acidified, which could be controlled by adding EDTA, a membrane-impermeable low molecular weight compound, during electrotransfection. With this method, we could then determine the precise structure and dynamics of proteins in endosomal vesicles. Our approach demonstrates that the combination of electrotransfection and in-cell NMR provides an opportunity to study the structural/dynamic features and physiological functions of molecules taken into intact cells.

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Section: Time-dependent Chemical Shift Changes Of In-cell Nmr Using E...supporting

confidence: 56%

Structure and Dynamics of a Protein Inside Endosomal Vesicles in Intact Human Cells

Kodama

Furuita

Sugiki

et al. 2022

Preprint

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“…The mechanisms of CPP penetration and CPP-cargo transport across the blood–brain barrier are discussed this year by Zorko and Langel [ 131 ]. Penetratin is usually linked with a drug, protein, or nucleic acid cargo at its N-terminal.…”

Section: Under-appreciated Versatility Of Penetratinsmentioning

confidence: 99%

Designed Multifunctional Peptides for Intracellular Targets

Juretić

2022

Antibiotics

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Nature’s way for bioactive peptides is to provide them with several related functions and the ability to cooperate in performing their job. Natural cell-penetrating peptides (CPP), such as penetratins, inspired the design of multifunctional constructs with CPP ability. This review focuses on known and novel peptides that can easily reach intracellular targets with little or no toxicity to mammalian cells. All peptide candidates were evaluated and ranked according to the predictions of low toxicity to mammalian cells and broad-spectrum activity. The final set of the 20 best peptide candidates contains the peptides optimized for cell-penetrating, antimicrobial, anticancer, antiviral, antifungal, and anti-inflammatory activity. Their predicted features are intrinsic disorder and the ability to acquire an amphipathic structure upon contact with membranes or nucleic acids. In conclusion, the review argues for exploring wide-spectrum multifunctionality for novel nontoxic hybrids with cell-penetrating peptides.

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“…As for the active penetration pathway, endocytosis can be further divided into phagocytosis and pinocytosis (including macropinocytosis, clathrin-mediated endocytosis, caveolae-mediated endocytosis, and clathrin- and caveolae-independent endocytosis). The detailed mechanism of CPP-cargo internalization is beyond the scope of this review, but can be read about in the newly published literature [ 56 , 80 , 81 , 94 , 95 ].…”

Section: Novel Pharmaceutical Strategies For Skin Penetrationmentioning

confidence: 99%

Novel Pharmaceutical Strategies for Enhancing Skin Penetration of Biomacromolecules

et al. 2022

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Skin delivery of biomacromolecules holds great advantages in the systemic and local treatment of multiple diseases. However, the densely packed stratum corneum and the tight junctions between keratinocytes stand as formidable skin barriers against the penetration of most drug molecules. The large molecular weight, high hydrophilicity, and lability nature of biomacromolecules pose further challenges to their skin penetration. Recently, novel penetration enhancers, nano vesicles, and microneedles have emerged as efficient strategies to deliver biomacromolecules deep into the skin to exert their therapeutic action. This paper reviews the potential application and mechanisms of novel skin delivery strategies with emphasis on the pharmaceutical formulations.

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Cell-Penetrating Peptides

Cited by 21 publications

References 167 publications

Structure and Dynamics of a Protein Inside Endosomal Vesicles in Intact Human Cells

Structure and Dynamics of a Protein Inside Endosomal Vesicles in Intact Human Cells

Designed Multifunctional Peptides for Intracellular Targets

Novel Pharmaceutical Strategies for Enhancing Skin Penetration of Biomacromolecules

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