Polyhistidine facilitates direct membrane translocation of cell-penetrating peptides into cells

Lee, Han-Jung; Huang, Yue-Wern; Chiou, Shiow-Her; Aronstam, Robert S.

doi:10.1038/s41598-019-45830-8

Cited by 34 publications

(32 citation statements)

References 45 publications

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“…However, some CPPs can enter the cell through either one of two path-ways (Figure 1). For example, recently published studies demonstrated that a bovine lactoferricin L6 CPP can be internalized by endocytosis, however the addition of polyhistidine peptides to this complex can also allow internalization by a direct membrane trans-location [24,25].…”

Section: Molecular Mechanisms Of Delivery Of Cell Penetrating Peptidesmentioning

confidence: 99%

Peptide-Based Drug Delivery Systems

et al. 2021

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Peptide-based drug delivery systems have many advantages when compared to synthetic systems in that they have better biocompatibility, biochemical and biophysical properties, lack of toxicity, controlled molecular weight via solid phase synthesis and purification. Lysosomes, solid lipid nanoparticles, dendrimers, polymeric micelles can be applied by intravenous administration, however they are of artificial nature and thus may induce side effects and possess lack of ability to penetrate the blood-brain barrier. An analysis of nontoxic drug delivery systems and an establishment of prospective trends in the development of drug delivery systems was needed. This review paper summarizes data, mainly from the past 5 years, devoted to the use of peptide-based carriers for delivery of various toxic drugs, mostly anticancer or drugs with limiting bioavailability. Peptide-based drug delivery platforms are utilized as peptide–drug conjugates, injectable biodegradable particles and depots for delivering small molecule pharmaceutical substances (500 Da) and therapeutic proteins. Controlled drug delivery systems that can effectively deliver anticancer and peptide-based drugs leading to accelerated recovery without significant side effects are discussed. Moreover, cell penetrating peptides and their molecular mechanisms as targeting peptides, as well as stimuli responsive (enzyme-responsive and pH-responsive) peptides and peptide-based self-assembly scaffolds are also reviewed.

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Section: Molecular Mechanisms Of Delivery Of Cell Penetrating Peptidesmentioning

confidence: 99%

Peptide-Based Drug Delivery Systems

et al. 2021

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“…The histamine-containing peptide 68 Ga-IMP-288 has been used for the pre-targeted PET imaging of carcinoembryonic antigen, which exhibited a quite low uptake in normal tissues [ 20 , 21 ]. In addition, several histidine-rich peptides have also been shown to exhibit high cell permeability and tumor accumulation properties [ 22 , 23 ]. Therefore, we also designed novel peptides in which the lysine residues of KV6 were replaced by arginine or histidine (RV6 and HV6, respectively), as shown in Figure 1 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Radiogallium-Labeled Cationic Amphiphilic Peptides as Tumor Imaging Agents

Fuchigami

Chiga

Yoshida

et al. 2021

Cancers

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SVS-1 is a cationic amphiphilic peptide (CAP) that exhibits a preferential cytotoxicity towards cancer cells over normal cells. In this study, we developed radiogallium-labeled SVS-1 (67Ga-NOTA-KV6), as well as two SVS-1 derivatives, with the repeating KV residues replaced by RV or HV (67Ga-NOTA-RV6 and 67Ga-NOTA-HV6). All three peptides showed high accumulation in epidermoid carcinoma KB cells (53–143% uptake/mg protein). Though 67Ga-NOTA-RV6 showed the highest uptake among the three CAPs, its uptake in 3T3-L1 fibroblasts was just as high, indicating a low selectivity. In contrast, the uptake of 67Ga-NOTA-KV6 and 67Ga-NOTA-HV6 into 3T3-L1 cells was significantly lower than that in KB cells. An endocytosis inhibition study suggested that the three 67Ga-NOTA-CAPs follow distinct pathways for internalization. In the biodistribution study, the tumor uptakes were found to be 4.46%, 4.76%, and 3.18% injected dose/g of tissue (% ID/g) for 67Ga-NOTA-KV6, 67Ga-NOTA-RV6, and 67Ga-NOTA-HV6, respectively, 30 min after administration. Though the radioactivity of these peptides in tumor tissue decreased gradually, 67Ga-NOTA-KV6, 67Ga-NOTA-RV6, and 67Ga-NOTA-HV6 reached high tumor/blood ratios (7.7, 8.0, and 3.8, respectively) and tumor/muscle ratios (5.0, 3.3, and 4.0, respectively) 120 min after administration. 67Ga-NOTA-HV6 showed a lower tumor uptake than the two other tracers, but it exhibited very low levels of uptake into peripheral organs. Overall, the replacement of lysine in SVS-1 with other basic amino acids significantly influenced its binding and internalization into cancer cells, as well as its in vivo pharmacokinetic profile. The high accessibility of these peptides to tumors and their ability to target the surface membranes of cancer cells make radiolabeled CAPs excellent candidates for use in tumor theranostics.

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“…TAT peptides are composed of 86 amino acids, among which the sequence of RKKKRRQRRR is known to be the minimum site for cell penetrating peptides. The experiments that substituted or deleted amino acid sequences of TAT peptides revealed that lysine (K) and arginine (R) play a key role in the intracellular permeability of TAT peptides as cell penetrating peptides [12][13][14][15][16]. Furthermore, since both the cell membrane and intercellular lipids have structural similarity in the structure of lipid bilayer, it is considered that the cell penetrating peptides can be applied to the intercellular lipids'permeation of functional materials [17][18].…”

Section: Introductionmentioning

confidence: 99%

A Clinical Study on Anti-wrinkle Efficacy of a Cosmetics Containing Oligoarginine Conjugation of Palmitoyl-GHK peptide for Skin Penetrating

Park¹,

Heo²,

Lee³

et al. 2021

TURCOMAT

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In this study, Arg 4 (R4) was conjugated with Pal-GHK to get palmitoyl heptapeptide, Pal-GHK‐R4 and wrinkle improvement clinical trials of cosmetics containing Pal-GHK‐R4 were conducted. As a result of total 21 subjects used the test products 4 weeks use on the face area; 1) measurement results of crow’s feet after 2 and 4 weeks of test products use, analysis value of crow’s feet statistically significantly decreased after 2 and 4 weeks of test products use compared to before use of products (p<0.05); 2) measurement results of skin moisturization after 2 and 4 weeks test products use, measured value of skin moisture content statistically significantly increased after 2 and 4 weeks use compared to before use of products (p<0.05); 3) measurement results of TEWL after 2 and 4 weeks use, measured value of TEWL statistically significantly decreased after 2 and 4 weeks use compared to before use of product(p<0.05); 4) there was no skin adverse event reported after using the products during the study period. Therefore, the test products containing both wrinkle improving and skin penetrating peptides, Pal-GHK‐R4 are considered to have beneficial effects on improvement of skin wrinkle, moisturization, transepidermal water loss(TEWL) after 2 and 4 weeks use of test product.

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Polyhistidine facilitates direct membrane translocation of cell-penetrating peptides into cells

Cited by 34 publications

References 45 publications

Peptide-Based Drug Delivery Systems

Peptide-Based Drug Delivery Systems

Synthesis and Characterization of Radiogallium-Labeled Cationic Amphiphilic Peptides as Tumor Imaging Agents

A Clinical Study on Anti-wrinkle Efficacy of a Cosmetics Containing Oligoarginine Conjugation of Palmitoyl-GHK peptide for Skin Penetrating

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