| 1. |
- Danielsson, Marie, 1981-, et al.
(författare)
-
Pharmacodynamic synergy strictly dependent on the co-operative aggregation of enantiomers of cyclic peptides in the bacterial cell membrane
- 2011
-
Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 21:18, s. 5262-5265
-
Tidskriftsartikel (refereegranskat)abstract
- The antimicrobial activity of the peptide enantiomers cyclo[d-Tle-d-Lys-d-Tle-l-Ala-d-Tle-l-Ala-d-Tle-l-Ala] and cyclo[l-Tle-l-Lys-l-Tle-d-Ala-l-Tle-d-Ala-l-Tle-d-Ala] against Bacillus megaterium was investigated. Both these peptides showed very low activity in both an agar diffusion assay and a broth microdilution assay. However, when both peptides were present during the experiments a potent inhibition with an IC(50) value of 2μM was observed. Furthermore, the peptides also showed low hemolytic activity. Neither peptide had any hemolytic activity in concentrations up to 1mM but when erythrocytes were exposed to both peptides a weak hemolytic activity could be observed with a HC(50) value of 316μM.
|
|
| 2. |
- Eiríksdóttir, Emelía, et al.
(författare)
-
An improved synthesis of releasable luciferin-CPP conjugates
- 2009
-
Ingår i: Tetrahedron Letters. - : Elsevier BV. - 0040-4039 .- 1359-8562. ; 50:33, s. 4731-4733
-
Tidskriftsartikel (refereegranskat)abstract
- We have improved the synthesis of a previously published luciferin-linker, used in an assay enabling rapid real-time quantification of luciferin–CPP conjugate uptake and cytosolic cargo release. We also present the synthesis of a new luciferin-linker with the same conjugation ability. Both luciferin-linkers are now available via an efficient one-pot procedure.
|
|
| 3. |
- EL Andaloussi, Samir, et al.
(författare)
-
Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo
- 2011
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 39:9, s. 3972-3987
-
Tidskriftsartikel (refereegranskat)abstract
- While small interfering RNAs (siRNAs) have been rapidly appreciated to silence genes, efficient and non-toxic vectors for primary cells and for systemic in vivo delivery are lacking. Several siRNA-delivery vehicles, including cell-penetrating peptides (CPPs), have been developed but their utility is often restricted by entrapment following endocytosis. Hence, developing CPPs that promote endosomal escape is a prerequisite for successful siRNA implementation. We here present a novel CPP, PepFect 6 (PF6), comprising the previously reported stearyl-TP10 peptide, having pH titratable trifluoromethylquinoline moieties covalently incorporated to facilitate endosomal release. Stable PF6/siRNA nanoparticles enter entire cell populations and rapidly promote endosomal escape, resulting in robust RNAi responses in various cell types (including primary cells), with minimal associated transcriptomic or proteomic changes. Furthermore, PF6-mediated delivery is independent of cell confluence and, in most cases, not significantly hampered by serum proteins. Finally, these nanoparticles promote strong RNAi responses in different organs following systemic delivery in mice without any associated toxicity. Strikingly, similar knockdown in liver is achieved by PF6/siRNA nanoparticles and siRNA injected by hydrodynamic infusion, a golden standard technique for liver transfection. These results imply that the peptide, in addition to having utility for RNAi screens in vitro, displays therapeutic potential.
|
|
| 4. |
- Hyvonen, Maija, et al.
(författare)
-
Novel Target for Peptide-Based Imaging and Treatment of Brain Tumors
- 2014
-
Ingår i: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 13:4, s. 996-1007
-
Tidskriftsartikel (refereegranskat)abstract
- Malignant gliomas are associated with high mortality due to infiltrative growth, recurrence, and malignant progression. Even with the most efficient therapy combinations, median survival of the glioblastoma multiforme (grade 4) patients is less than 15 months. Therefore, new treatment approaches are urgently needed. We describe here identification of a novel homing peptide that recognizes tumor vessels and invasive tumor satellites in glioblastomas. We demonstrate successful brain tumor imaging using radiolabeled peptide in whole-body SPECT/CT imaging. Peptide-targeted delivery of chemotherapeutics prolonged the lifespan of mice bearing invasive brain tumors and significantly reduced the number of tumor satellites compared with the free drug. Moreover, we identified mammary-derived growth inhibitor (MDGI/H-FABP/FABP3) as the interacting partner for our peptide on brain tumor tissue. MDGI was expressed in human brain tumor specimens in a grade-dependent manner and its expression positively correlated with the histologic grade of the tumor, suggesting MDGI as a novel marker for malignant gliomas. Mol Cancer Ther; 13(4); 996-1007. (C)2014 AACR.
|
|
| 5. |
- Lindgren, Maria, et al.
(författare)
-
Overcoming methotrexate resistance in breast cancer tumour cells by the use of a new cell-penetrating peptide
- 2006
-
Ingår i: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839. ; 71:4, s. 416-425
-
Tidskriftsartikel (refereegranskat)abstract
- Resistance to chemotherapy limits the effectiveness of anti-cancer drug treatment. Here, we present a new approach to overcome the setback of drug resistance by designing a conjugate of a cell-penetrating peptide and the cytostatic agent methotrexate (MTX). Two different peptides, YTA2 and YTA4, were designed and their intracellular delivery efficiency was characterized by fluorescence microscopy and quantified by fluorometry. MTX was conjugated to the transport peptides and the ability of the peptide–MTX conjugates to inhibit dihydrofolate reductase, the target enzyme of MTX, was found to be 15 and 20 times less potent than MTX. In addition, in vitro studies were performed in a drug resistant cell model using the 100-fold MTX resistant breast cancer cells MDA-MB-231. At a concentration of 1 mM, the peptide–MTX conjugates were shown to overcome MTX resistance and kill the cells more efficiently than MTX alone. Estimated EC50’s were determined for MTX, MTXYTA2 and YTA2 to be 18.5, 3.8 and 20 µM, respectively. In summary, cell-penetrating peptide conjugation of MTX is a new way of increasing delivery, and thereby, the potency of already well-characterized therapeutic molecules into drug resistant tumour cells.
|
|
| 6. |
- Mae, Maarja, et al.
(författare)
-
Tumour targeting with rationally modified cell penetrating peptides
- 2012
-
Ingår i: International Journal of Peptide Research and Therapeutics. - : Springer Science and Business Media LLC. - 1573-3149 .- 1573-3904. ; 18:4, s. 361-371
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-penetrating peptides (CPPs) are short transport peptides with a well-established ability for delivery of bioactive cargoes inside the cells both, in vitro and in vivo. CPPs enter unselectively in a wide variety of cell lines, this is a desirable property for most in vitro applications, however, in vivo e.g. in tumor models, specific targeted accumulation is required. In order to achieve tumor targeting, a known CPP, YTA4, was modified by prolonging it C-terminally with mainly negatively charged amino acids. Additionally, a matrix metalloproteinase-2 cleavage site was introduced between the CPP and the inactivating sequence. This new peptide, named NoPe, is an inactive pro-form of YTA4. It can be selectively cleaved and thereby activated by MMPs. We have conjugated an imaging agent, fluoresceinyl carboxylic acid, and a cytostatic agent methotrexate, to this activable pro-form. NoPe activation was demonstrated in vitro by recombinant MMP-2 cleavage and the cleavage of the attenuating sequence was abolished with MMP-2 specific inhibitor. Furthermore, the fluoresceinyl-NoPe is selectively accumulated in the tumor tissue in MDA-MB-231 tumor bearing mice after intravenous injection. Thus, this strategy proves to be successful for in vivo tumor imaging.
|
|
| 7. |
|
|
| 8. |
- Rosenthal-Aizman, Katri, et al.
(författare)
-
Self-assembling peptide nanotubes from enantiomeric pairs of cyclic peptides with alternating D and L amino acid residues
- 2004
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 126:11, s. 3372-3373
-
Tidskriftsartikel (refereegranskat)abstract
- Cyclic peptides with alternating d- and l-amino acid residues containing tert-leucine residues in every second position can form peptide nanotubes only when both enantiomers of the peptide are present in the solution. These results strongly indicate the formation of peptide nanotubes that assemble with one enantiomer in every second position, thereby forming a lamellar structure.
|
|
| 9. |
|
|
| 10. |
- Saar, Külliki, et al.
(författare)
-
Cell-Penetrating Peptides : A Comparative Membrane Toxicity Study
- 2005
-
Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 345:1, s. 55-65
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-penetrating peptides (CPPs) constitute a new class of delivery vectors with high pharmaceutical potential. However, the abilities of these peptides to translocate through cell membranes can be accompanied by toxic effects resulting from membrane perturbation at higher peptide concentrations. Therefore, we investigated membrane toxicity of five peptides with well-documented cell-penetrating properties, pAntp(43–58), pTAT(48–60), pVEC(615–632), model amphipathic peptide (MAP), and transportan 10, on two human cancer cell lines, K562 (erythroleukemia) and MDA-MB-231 (breast cancer), as well as on immortalized aortic endothelial cells. We studied the effects of these five peptides on the leakage of lactate dehydrogenase and on the fluorescence of plasma membrane potentiometric dye bis-oxonol. In all cell lines, pAntp(43–58), pTAT(48–60), and pVEC(615–632) induced either no leakage or low leakage of lactate dehydrogenase, accompanied by modest changes in bis-oxonol fluorescence. MAP and transportan 10 caused significant leakage; in K562 and MDA-MB-231 cells, 40% of total lactate dehydrogenase leaked out during 10 min exposure to 10 μM of transportan 10 and MAP, accompanied by a significant increase in bis-oxonol fluorescence. However, none of the CPPs tested had a hemolytic effect on bovine erythrocytes comparable to mastoparan 7. The toxicity profiles presented in the current study are of importance when selecting CPPs for different applications.
|
|
