| 1. |
- Anko, Maja, et al.
(författare)
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Influence of stearyl and trifluoromethylquinoline modifications of the cell penetrating peptide TP10 on its interaction with a lipid membrane
- 2012
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642. ; 1818:3, s. 915-924
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Tidskriftsartikel (refereegranskat)abstract
- The PepFect family of cell-penetrating peptides (CPPs) was designed to improve the delivery of nucleic acids across plasma membranes. We present here a comparative study of two members of the family, PepFect3 (PF3) and PepFect6 (PF6), together with their parental CPP transportan-10 (TP10), and their interactions with lipid membranes. We show that the addition of a stearyl moiety to TP10 increases the amphipathicity of these molecules and their ability to insert into a lipid monolayer composed of zwitterionic phospholipids. The addition of negatively charged phospholipids into the monolayer results in decreased binding and insertion of the stearylated peptides, indicating modification in the balance of hydrophobic versus electrostatic interactions of peptides with lipid bilayer, thus revealing some clues for the selective interaction of these CPPs with different lipids. The trifluoromethylquinoline moieties, in PF6 make no significant contribution to membrane binding and insertion. TP10 actively introduces pores into the bilayers of large and giant unilamellar vesicles, while PF3 and PF6 do so only at higher concentrations. This is consistent with the lower toxicity of PR and PF6 observed in previous studies.
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| 2. |
- Arsov, Zoran, et al.
(författare)
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Cholesterol prevents interaction of the cell-penetrating peptide transportan with model lipid membranes
- 2008
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Ingår i: Journal of Peptide Science. - : Wiley. - 1075-2617 .- 1099-1387. ; 14:12, s. 1303-1308
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Tidskriftsartikel (refereegranskat)abstract
- Interaction of the cell-penetrating peptide (CPP) cysteine-transportan (Cys-TP) with model lipid membranes was examined by spin-label electron paramagnetic resonance (EPR). Membranes were labeled with lipophilic spin probes and the influence of Cys-TP on membrane structure Was studied. The influence of Cys-TP on membrane permeability was monitored by the reduction of a liposome-trapped water-soluble spin probe. Cys-TP caused lipid ordering in membranes prepared from pure dimyristoylphosphatidylcholine (DMPC) and in DMPC membranes with moderate cholesterol concentration. In addition, Cys-TP caused a large increase in permeation of DMPC membranes. In contrast, with high cholesterol content, at which model lipid membranes are in the so-called liquid-ordered phase, no effect. of Cys-TP was observed, either on Line membrane structure or on the membrane permeability. The interaction between Cys-TP and the lipid membrane therefore depends on the lipid phase. This could be of great. importance for understanding of the CPP-lipid interaction in laterally heterogeneous membranes, white it implies that the CPP-lipid interaction can be different at different points along the membrane.
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| 3. |
- Bavec, Aljosa, et al.
(författare)
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Role of cysteine 341 and arginine 348 of GLP-1 receptor in G-protein coupling
- 2007
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 34:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- We have demonstrated the ability of peptides derived from the third intracellular loop of GLP-1 receptor to differently modulate activity of four different types of G-proteins overexpressed in sf9 cells. In this respect, the involvement of Cys341 in inhibition of Gs and Cys341 in activation of Gs and in inhibition of Gi1, Go, and G11, respectively, indicates their potential role in discrimination between different types of G-proteins. Moreover, these two amino acids from the third intracellular loop might represent an important novel targets for covalent modification by downstream regulators in signaling through GLP-1 receptor.
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| 4. |
- Howl, John, et al.
(författare)
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Bioportide : an emergent concept of bioactive cell penetrating peptides
- 2012
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 69:17, s. 2951-2966
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Tidskriftsartikel (refereegranskat)abstract
- Cell-penetrating peptides (CPPs) have proven utility for the highly efficient intracellular delivery of bioactive cargoes that include peptides, proteins, and oligonucleotides. The many strategies developed to utilize CPPs solely as pharmacokinetic modifiers necessarily requires them to be relatively inert. Moreover, it is feasible to combine one or multiple CPPs with bioactive cargoes either by direct chemical conjugation or, more rarely, as non-covalent complexes. In terms of the message-address hypothesis, this combination of cargo (message) linked to a CPP (address) as a tandem construct conforms to the sychnological organization. More recently, we have introduced the term bioportide to describe monomeric CPPs that are intrinsically bioactive. Herein, we describe the design and biochemical properties of two rhegnylogically organized monometic CPPs that collectively modulate a variety of biological and pathophysiological phenomena. Thus, camptide, a cell-penetrant sequence located within the first intracellular loop of a human calcitonin receptor, regulates cAMP-dependent processes to modulate insulin secretion and viral infectivity. Nosangiotide, a bioportide derived from endothelial nitric oxide synthase, potently inhibits many aspects of the endothelial cell morphology and movement and displays potent anti-angiogenic activity in vivo. We conclude that, due to their capacity to translocate and target intracellular signaling events, bioportides represent an innovative generic class of bioactive agents.
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| 5. |
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| 6. |
- Zorko, Matjaž, et al.
(författare)
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Cell-Penetrating Peptides
- 2022. - 3
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Ingår i: Cell Penetrating Peptides. - New York : Humana Press. - 9781071617519 - 9781071617526 ; , s. 3-32
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Bokkapitel (refereegranskat)abstract
- In this introductory chapter, we first define cell-penetrating peptides (CPPs), give short overview of CPP history and discuss several aspects of CPP classification. Next section is devoted to the mechanism of CPP penetration into the cells, where direct and endocytic internalization of CPP is explained. Kinetics of internalization is discussed more extensively, since this topic is not discussed in other chapters of this book. At the end of this section some features of the thermodynamics of CPP interaction with the membrane is also presented. Finally, we present different cargoes that can be transferred into the cells by CPPs and briefly discuss the effect of cargo on the rate and efficiency of penetration into the cells.
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| 7. |
- Zorko, Matjaž, et al.
(författare)
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Cell-penetrating peptides in protein mimicry and cancer therapeutics
- 2022
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Ingår i: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 180
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Forskningsöversikt (refereegranskat)abstract
- Extensive research has been undertaken in the pursuit of anticancer therapeutics. Many anticancer drugs require specificity of delivery to cancer cells, whilst sparing healthy tissue. Cell-penetrating peptides (CPPs), now well established as facilitators of intracellular delivery, have in recent years advanced to incorporate target specificity and thus possess great potential for the targeted delivery of anticancer cargoes. Though none have yet been approved for clinical use, this novel technology has already entered clinical trials. In this review we present CPPs, discuss their classification, mechanisms of cargo internalization and highlight strategies for conjugation to anticancer moieties including their incorporation into therapeutic proteins. As the mainstay of this review, strategies to build specificity into tumor targeting CPP constructs through exploitation of the tumor microenvironment and the use of tumor homing peptides are discussed, whilst acknowledging the extensive contribution made by CPP constructs to target specific protein-protein interactions integral to intracellular signaling pathways associated with tumor cell survival and progression. Finally, antibody/antigen CPP conjugates and their potential roles in cancer immunotherapy and diagnostics are considered. In summary, this review aims to harness the potential of CPP-aided drug delivery for future cancer therapies and diagnostics whilst highlighting some of the most recent achievements in selective delivery of anticancer drugs, including cytostatic drugs, to a range of tumor cells both in vitro and in vivo.
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| 8. |
- Zorko, Matjaž, et al.
(författare)
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Studies of cell-penetrating peptides by biophysical methods
- 2022
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Ingår i: Quarterly reviews of biophysics (Print). - 0033-5835 .- 1469-8994. ; 55
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Forskningsöversikt (refereegranskat)abstract
- Biophysical studies have a very high impact on the understanding of internalization, molecular mechanisms, interactions, and localization of CPPs and CPP/cargo conjugates in live cells or in vivo. Biophysical studies are often first carried out in test-tube set-ups or in vitro, leading to the complicated in vivo systems. This review describes recent studies of CPP internalization, mechanisms, and localization. The multiple methods in these studies reveal different novel and important aspects and define the rules for CPP mechanisms, hopefully leading to their improved applicability to novel and safe therapies.
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