Refinement of a Quantitative Structure–Activity Relationship Model for Prediction of Cell-Penetrating Peptide Based Transfection Systems

Dowaidar, Moataz; Regberg, Jakob; Dobchev, Dimitar A.; Lehto, Tõnis; Hällbrink, Mattias; Karelson, Mati; Langel, Ülo

doi:10.1007/s10989-016-9542-8

Cited by 19 publications

(22 citation statements)

References 23 publications

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“…Cell-penetrating peptides (CPPs) are short cationic peptides that have the capability of delivering cargos across cellular membranes with low toxicity 2 – 4 . The uptake pathways of CPPs are not entirely understood, and even less is known about the cellular responses and intracellular trafficking of CPP-cargo constructs.…”

Section: Introductionmentioning

confidence: 99%

Role of autophagy in cell-penetrating peptide transfection model

Dowaidar

Gestin

Cerrato

et al. 2017

Sci Rep

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Cell-penetrating peptides (CPPs) uptake mechanism is still in need of more clarification to have a better understanding of their action in the mediation of oligonucleotide transfection. In this study, the effect on early events (1 h treatment) in transfection by PepFect14 (PF14), with or without oligonucleotide cargo on gene expression, in HeLa cells, have been investigated. The RNA expression profile was characterized by RNA sequencing and confirmed by qPCR analysis. The gene regulations were then related to the biological processes by the study of signaling pathways that showed the induction of autophagy-related genes in early transfection. A ligand library interfering with the detected intracellular pathways showed concentration-dependent effects on the transfection efficiency of splice correction oligonucleotide complexed with PepFect14, proving that the autophagy process is induced upon the uptake of complexes. Finally, the autophagy induction and colocalization with autophagosomes have been confirmed by confocal microscopy and transmission electron microscopy. We conclude that autophagy, an inherent cellular response process, is triggered by the cellular uptake of CPP-based transfection system. This finding opens novel possibilities to use autophagy modifiers in future gene therapy.

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Section: Introductionmentioning

confidence: 99%

Role of autophagy in cell-penetrating peptide transfection model

Dowaidar

Gestin

Cerrato

et al. 2017

Sci Rep

Self Cite

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“…Several criteria have been chosen to evaluate the quality of those models, including the total number of compounds applied in the training dataset, results of the correlation coefficients; and standard error estimation (Neves et al, 2018). The QSPR models have been applied to evaluate the penetration of different classes of compounds into the biomembranes, including the cell membrane (Dowaidar et al, 2017) and the BBB (Zhang et al, 2008;Fan et al, 2010;Bujak et al, 2015). The QSPR models that predict the penetration of compounds into BBB use some experimental parameters applied to evaluate the penetration, such as logBB and logPS (Nikolic et al, 2013).…”

Section: Quantitative Structure-property Relationshipsmentioning

confidence: 99%

Biological Membrane-Penetrating Peptides: Computational Prediction and Applications

Oliveira

Costa

Taube

et al. 2022

Front. Cell. Infect. Microbiol.

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Peptides comprise a versatile class of biomolecules that present a unique chemical space with diverse physicochemical and structural properties. Some classes of peptides are able to naturally cross the biological membranes, such as cell membrane and blood-brain barrier (BBB). Cell-penetrating peptides (CPPs) and blood-brain barrier-penetrating peptides (B3PPs) have been explored by the biotechnological and pharmaceutical industries to develop new therapeutic molecules and carrier systems. The computational prediction of peptides’ penetration into biological membranes has been emerged as an interesting strategy due to their high throughput and low-cost screening of large chemical libraries. Structure- and sequence-based information of peptides, as well as atomistic biophysical models, have been explored in computer-assisted discovery strategies to classify and identify new structures with pharmacokinetic properties related to the translocation through biomembranes. Computational strategies to predict the permeability into biomembranes include cheminformatic filters, molecular dynamics simulations, artificial intelligence algorithms, and statistical models, and the choice of the most adequate method depends on the purposes of the computational investigation. Here, we exhibit and discuss some principles and applications of these computational methods widely used to predict the permeability of peptides into biomembranes, exhibiting some of their pharmaceutical and biotechnological applications.

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“…There have also been cases of ichthyosis coupled with widespread and resistant fungal infections (3,7,11,13,17,18). Technology advancements have expanded study into the causes of fungal infection in ichthyosis patients (19), and a link between genotype and susceptibility to fungal infection has been postulated (20). Given that > 40% of patients with such mutations had fungal infections, several researchers hypothesized that individuals with ARCI caused by mutations in SDR9C7 were prone to recurrent fungal skin infections (20,21).…”

Section: Fungal Infections and Non-syndromic Ichthyosesmentioning

confidence: 99%

Gene therapy may benefit inherited ichthyoses with concurrent fungal infections and severe ich thyroidoses

Dowaidar¹

2021

Preprint

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Despite the fact that inherited ichthyoses with simultaneous fungal infections have been documented for more than 50 years, the connection between the two remains unknown. Because ichthyosis makes it harder to identify a concurrent fungal infection, it's important to pay close attention to prevent missing or delaying a diagnosis. The underlying ichthyosis makes treating fungal infections more difficult, and severe and recurrent infections need further attention. Those with severe ichthyoses may benefit from gene therapy in order to avoid fungal infection. More clinical and laboratory research is needed, however, to fully comprehend the mechanisms of action and provide a foundation of knowledge from which innovative therapy alternatives might be created.

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Refinement of a Quantitative Structure–Activity Relationship Model for Prediction of Cell-Penetrating Peptide Based Transfection Systems

Cited by 19 publications

References 23 publications

Role of autophagy in cell-penetrating peptide transfection model

Role of autophagy in cell-penetrating peptide transfection model

Biological Membrane-Penetrating Peptides: Computational Prediction and Applications

Gene therapy may benefit inherited ichthyoses with concurrent fungal infections and severe ich thyroidoses

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