Cell penetrating peptides: Highlighting points in cancer therapy

Asrorov, Akmal M.; Wang, Huiyuan; Zhang, Meng; Wang, Yonghui; He, Yue; Sharipov, Mirkomil; Yili, Abulimiti; Huang, Yongzhuo

doi:10.1002/ddr.22076

Cited by 10 publications

(2 citation statements)

References 266 publications

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“…A linker is frequently used in order to increase the distance between the peptide and the active ingredient or providing reversibility (capability of detachment under appropriate conditions) [ 9 , 10 , 11 , 12 , 13 ]. CPPs also can be the component of more complex drug delivery systems combined with polymers, dendrimers, or antibodies for targeting, especially in cancer therapy [ 14 , 15 ]. Homing peptides and targeting ligands are capable of combining with CPPs to improve cell specificity [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulations of Drug-Conjugated Cell-Penetrating Peptides

Ivánczi,

Balogh,

Kis

et al. 2023

Pharmaceuticals

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Cell-penetrating peptides (CPPs) are small peptides capable of translocating through biological membranes carrying various attached cargo into cells and even into the nucleus. They may also participate in transcellular transport. Our in silico study intends to model several peptides and their conjugates. We have selected three CPPs with a linear backbone, including penetratin, a naturally occurring oligopeptide; two of its modified sequence analogues (6,14-Phe-penetratin and dodeca-penetratin); and three natural CPPs with a cyclic backbone: Kalata B1, the Sunflower trypsin inhibitor 1 (SFT1), and Momordica cochinchinensis trypsin inhibitor II (MCoTI-II). We have also built conjugates with the small-molecule drug compounds doxorubicin, zidovudine, and rasagiline for each peptide. Molecular dynamics (MD) simulations were carried out with explicit membrane models. The analysis of the trajectories showed that the interaction of penetratin with the membrane led to spectacular rearrangements in the secondary structure of the peptide, while cyclic peptides remained unchanged due to their high conformational stability. Membrane–peptide and membrane–conjugate interactions have been identified and compared. Taking into account well-known examples from the literature, our simulations demonstrated the utility of computational methods for CPP complexes, and they may contribute to a better understanding of the mechanism of penetration, which could serve as the basis for delivering conjugated drug molecules to their intracellular targets.

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Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulations of Drug-Conjugated Cell-Penetrating Peptides

Ivánczi,

Balogh,

Kis

et al. 2023

Pharmaceuticals

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“…Нами использован подход создания новых противоопухолевых препаратов, базирующийся на инновационной технологии внутриклеточной доставки высокомолекулярных соединений на основе СРР (англ. cell penetrating peptides), или интернализуемых пептидов [8,9]. Лекарственное средство Инг-Рас представляет собой химерный пептид, содержащий транспортный фрагмент (последовательность СРР) и функциональный фрагмент (аминокислотная последовательность, связывающаяся с белком RAS).…”

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Safety assessment and determination of a maximally tolerated dose of an RAS-GTPase inhibitor (iRAS) in the treatment of gastrointestinal tumors: preliminary results of the phase I trial

Bozhenko,

Goncharov,

Kudinova

et al. 2024

Almanac of Clinical Medicine

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Background: Ras oncogene mutations leading to hyperactivation of the MAPK/ERK signaling pathway occur in 25% of all human tumors, and for gastrointestinal tumors, the frequency of Ras mutations amounts to 60%. The introduction of a Ras-GTPase inhibitor into clinical practice would increase the effectiveness of the treatment of socially significant diseases such as stomach and intestinal cancer. Aim: To select the optimal dose with a subsequent assessment of the safety of iRAS when administered to patients with gastrointestinal tract tumors, including those with peritoneal carcinomatosis. Materials and methods: This was a prospective open-label non-randomized phase I study for the assessment of safety and tolerability, with an adaptive design and determination of the maximally tolerated dose of the iRAS. Three dose levels were used (0.45 mg/kg, 0.9 mg/kg, 1.8 mg/kg) according to the "3 + 3" scheme. The study included 11 patients after surgery for stomach or colorectal cancer. The patients were administered PIPAC therapy with iRAS twice with a 7-days interval. The study duration was 28 ± 1 days. During the study, the patient monitoring included physical examination, assessment of vital signs, electrocardiography and echocardiography, laboratory parameters (hematology, clinical chemistry, coagulation tests, and urine analysis). Results: The anti-tumor iRAS agent demonstrated satisfactory tolerability of all doses studied, including the maximal 1.8 mg/kg dose. Vital sign and laboratory abnormalities were clinically non-significant and did not require additional therapeutic interventions. Statistically significant abnormalities were registered for total protein (p = 0.00028), white blood cell counts (p = 0.007), lymphocyte counts (p = 0.0008), and a number of other blood parameters; however, most of these abnormalities were within the physiological normal ranges. Vital signs such as electrocardiography and echocardiography parameters remained stable throughout the entire follow-up period (28 days after administration of the drug). There were short-term rises in body temperature, minor pains in the postoperative scar area. Conclusion: This trial of safety and tolerability of iRAS showed that no cases of dose-limiting toxicity in the studied dose range. The 1.8 mg/kg dose can be recommended for further clinical studies.

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Food Protein‐Derived Zinc‐Binding Peptides: Isolation, Purification, and Biological Aspects

Mukhamedov,

Asrorov,

Kayumov

et al. 2024

Peptide Science

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Zinc is the second most valuable microelement after iron, according to its abundance in the human body. Supplementation of this metal is not straightforward because of several factors like phytates and interference of other minerals during gastrointestinal digestion. For the last several years, intensive research has been developing new forms of zinc supplements based on zinc‐binding peptides from food products. Except for the advantages of supplementation, zinc‐peptide complexes are expected to be drug candidates against various diseases. Zinc supplementation can be improved by protein hydrolysates and peptides due to their zinc‐binding ability. They enhance zinc supplementation and contribute to preventing conditions leading to zinc deficiency that cause various diseases. Research on food‐derived zinc‐binding peptides is progressing in two directions: the isolation and identification of individual peptides (1) and the preparation of zinc complexes of protein hydrolysates (2). Both approaches are primarily aimed at developing effective mineral supplements, although some work on the second approach is also related to nutrition and therapy. Because zinc–protein hydrolysate complexes are nonstandardized mixtures of peptides, their biological activity mechanisms can be difficult to study. Therefore, it is important to focus more research on the biological activity of individual zinc‐binding complexes and their zinc complexes. This work reviewed recent advances in isolating and identifying zinc‐binding peptides from food sources, preparing protein hydrolysate–zinc complexes, and their biological activities. The established sequences of zinc‐binding peptides have been compiled into a table to review their amino‐acid composition and sequence. We also highlighted approaches for isolating and determining the zinc‐binding capacity of peptides in this class. The structural features of peptides affecting their zinc‐binding property were discussed in one section.

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Cell penetrating peptides: Highlighting points in cancer therapy

Cited by 10 publications

References 266 publications

Molecular Dynamics Simulations of Drug-Conjugated Cell-Penetrating Peptides

Molecular Dynamics Simulations of Drug-Conjugated Cell-Penetrating Peptides

Safety assessment and determination of a maximally tolerated dose of an RAS-GTPase inhibitor (iRAS) in the treatment of gastrointestinal tumors: preliminary results of the phase I trial

Food Protein‐Derived Zinc‐Binding Peptides: Isolation, Purification, and Biological Aspects

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