TargetCPP: accurate prediction of cell-penetrating peptides from optimized multi-scale features using gradient boost decision tree

Arif, Muhammad; Ahmad, Saeed; Ali, Farman; Ge, Fang; Li, Min; Yu, Dong‐Jun

doi:10.1007/s10822-020-00307-z

Cited by 51 publications

(26 citation statements)

References 91 publications

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“…In addition, identifying shorter sequences is of great value when taking easier synthesis pathways and lower production costs into account. Importantly, computational methods attract more and more notice to predict novel CPP sequences [111].…”

Section: Current State-of-the-art and Future Perspectivesmentioning

confidence: 99%

Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

Gessner

Neundorf

2020

IJMS

144

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Based on their tunable physicochemical properties and the possibility of producing cell-specific platforms through surface modification with functional biomolecules, nanoparticles (NPs) represent highly promising tools for biomedical applications. To improve their potential under physiological conditions and to enhance their cellular uptake, combinations with cell-penetrating peptides (CPPs) represent a valuable strategy. CPPs are often cationic peptide sequences that are able to translocate across biological membranes and to carry attached cargos inside cells and have thus been recognized as versatile tools for drug delivery. Nevertheless, the conjugation of CPP to NP surfaces is dependent on many properties from both individual components, and further insight into this complex interplay is needed to allow for the fabrication of highly stable but functional vectors. Since CPPs per se are nonselective and enter nearly all cells likewise, additional decoration of NPs with homing devices, such as tumor-homing peptides, enables the design of multifunctional platforms for the targeted delivery of chemotherapeutic drugs. In this review, we have updated the recent advances in the field of CPP-NPs, focusing on synthesis strategies, elucidating the influence of different physicochemical properties, as well as their application in cancer research.

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Section: Current State-of-the-art and Future Perspectivesmentioning

confidence: 99%

Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

Gessner

Neundorf

2020

IJMS

144

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“…Numerous studies have suggested that applying bioinformatic tools for CPP predictions prior to wet-lab experimental characterization can save time and money (Arif et al, 2020 ; Kardani and Bolhassani, 2021 ). Therefore, in this study, we combined bioinformatic prediction and experimental validation to find and characterize novel and potent CPPs as a DNA vaccine and drug delivery system.…”

Section: Introductionmentioning

confidence: 99%

In silico identification and experimental validation of cellular uptake by a new cell penetrating peptide P1 derived from MARCKS

et al. 2021

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Viral vectors for vaccine delivery are challenged by recently reported safety issues like immunogenicity and risk for cancer development, and thus there is a growing need for the development of non-viral vectors. Cell penetrating peptides (CPPs) are non-viral vectors that can enter plasma membranes efficiently and deliver a broad range of cargoes. Our bioinformatic prediction and wet-lab validation data suggested that peptide P1 derived from MARCKS protein phosphorylation site domain is a new potential CPP candidate. We found that peptide P1 can efficiently internalize into various cell lines in a concentration-dependent manner. Receptor-mediated endocytosis pathway is the major mechanism of P1 penetration, although P1 also directly penetrates the plasma membrane. We also found that peptide P1 has low cytotoxicity in cultured cell lines as well as mouse red blood cells. Furthermore, peptide P1 not only can enter into cultured cells itself, but it also can interact with plasmid DNA and mediate the functional delivery of plasmid DNA into cultured cells, even in hard-to-transfect cells. Combined, these findings indicate that P1 may be a promising vector for efficient intracellular delivery of bioactive cargos.

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“…Notably, computational methods are receiving increasing attention in predicting novel CPP sequences. [261][262][263] Substantial efforts have been made to design and modulate novel CPP sequences, exhibiting increased membrane permeability and improved target specificity. Quantitative analysis tracking non-fragmented peptide drugs has a high possibility to contribute to the development of CPP-based therapeutic.…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

The role of cell‐penetrating peptides in potential anti‐cancer therapy

Zhou

Zou

Cheng

et al. 2022

Clinical & Translational Med

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Due to the complex physiological structure, microenvironment and multiple physiological barriers, traditional anti‐cancer drugs are severely restricted from reaching the tumour site. Cell‐penetrating peptides (CPPs) are typically made up of 5–30 amino acids, and can be utilised as molecular transporters to facilitate the passage of therapeutic drugs across physiological barriers. Up to now, CPPs have widely been used in many anti‐cancer treatment strategies, serving as an excellent potential choice for oncology treatment. However, their drawbacks, such as the lack of cell specificity, short duration of action, poor stability in vivo, compatibility problems (i.e. immunogenicity), poor therapeutic efficacy and formation of unwanted metabolites, have limited their further application in cancer treatment. The cellular uptake mechanisms of CPPs involve mainly endocytosis and direct penetration, but still remain highly controversial in academia. The CPPs‐based drug delivery strategy could be improved by clever design or chemical modifications to develop the next‐generation CPPs with enhanced cell penetration capability, stability and selectivity. In addition, some recent advances in targeted cell penetration that involve CPPs provide some new ideas to optimise CPPs.

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TargetCPP: accurate prediction of cell-penetrating peptides from optimized multi-scale features using gradient boost decision tree

Cited by 51 publications

References 91 publications

Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy

In silico identification and experimental validation of cellular uptake by a new cell penetrating peptide P1 derived from MARCKS

The role of cell‐penetrating peptides in potential anti‐cancer therapy

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