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Protein delivery by the cell-penetrating peptide YTA2
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0001-6107-0844
2007 (English)In: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 18, no 1, 170-174 p.Article in journal (Refereed) Published
Abstract [en]

In most cases, the transport of cell-penetrating peptide (CPP) with a cargo molecule over the plasma membrane requires a cross-linking of the cargo molecule to the peptide. Lately, a method of cargo delivery, coincubation with CPP, has been applied. We have studied uptake and toxicity of the CPP, YTA2, in the Bowes human melanoma cell line and human MDA-MB-231 breast cancer cell line and compared the results with known cell-penetrating peptides. The results show that fluoresceinyl YTA2 is taken up by the Bowes cells with 3.23 nmol/mg protein and shows low membrane toxicity to the cells with an EC50 of 60 μM. Furthermore, we show that YTA2 is capable of delivering cargo proteins, such as β-galactosidase and tetramethyl rhodamine iso-thiocyanate (TRITC) labeled streptavidin into cells by coincubation. The delivery of TRITC-labeled streptavidin was quantified to 42.4 pmol streptavidin/mg protein. The delivery of proteins into the cells by mere coincubation is an advantage, since the chemical coupling between the CPP and the cargo molecule, which adds time-consuming synthesis and purification steps, can be omitted. In addition, the flexibility in CPP cargo delivery is increased.

Place, publisher, year, edition, pages
2007. Vol. 18, no 1, 170-174 p.
National Category
Biological Sciences Chemical Sciences
Identifiers
URN: urn:nbn:se:su:diva-20830DOI: 10.1021/bc060266gISI: 000243503400022OAI: oai:DiVA.org:su-20830DiVA: diva2:187356
Available from: 2008-01-14 Created: 2008-01-14 Last updated: 2015-04-21Bibliographically approved
In thesis
1. Cell-penetrating peptides in cargo delivery: In vitro studies on uptake and in vivo studies on tumor targeting
Open this publication in new window or tab >>Cell-penetrating peptides in cargo delivery: In vitro studies on uptake and in vivo studies on tumor targeting
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The capability of cell-penetrating peptides (CPPs) to transport cargos over different cellular membranes both in vitro and in vivo have drawn major attention in the past decade. Three main topics on the application of CPPs have been studied in this thesis.

First, several well-known CPPs, with fluorescein as a cargo, were shown to translocate into Nicotiana tabacum cultivar SR-1 protoplasts. By coupling different cargos to CPP it might be possible to effectively transport them inside the plant protoplasts. The translocation of CPPs into plant protoplasts might open up a new method for transformation of plant cells.

Next, the cell-penetrating ability of the novel peptide YTA2 was characterized and it was established that chemical coupling between YTA2 and the protein cargo is not needed for the transport of the cargo over the cellular membrane in vitro. The delivery of proteins into cells by mere coincubation with CPPs is an improvement, since the chemical coupling between the CPP and the cargo molecule, which adds time-consuming synthesis and purification steps, can be omitted.

Finally, by conjugating each of the two breast tumor homing peptides, the cyclic cCPGPEGAGC (PEGA) or the linear CREKA peptide, to the CPP pVEC, two cell-penetrating peptides with homing properties were obtained. Both, PEGA-pVEC and CREKA-pVEC were taken up by different breast cancer cells in vitro. Moreover, the homing capacity of the PEGA-pVEC and CREKA-pVEC was conserved in vivo, where the conjugates mainly accumulated in blood vessels in breast tumor tissue and were subsequently translocated into cells. Conjugating the anti-cancer drug chlorambucil to PEGA-pVEC or CREKA-pVEC markedly improved its efficiency. Furthermore, systemic treatment of tumor-bearing mice with chlorambucil-CREKA-pVEC significantly reduced tumor growth compared to control groups. These tumor-homing CPPs might improve both diagnosis and treatment of breast cancer tumors, by conjugation to therapeutic agents.

Place, publisher, year, edition, pages
Stockholm: Institutionen för neurokemi, 2008. 67 p.
National Category
Neurosciences
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
urn:nbn:se:su:diva-7263 (URN)978-91-7155-554-0 (ISBN)
Public defence
2008-02-01, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 10:00
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Available from: 2008-01-10 Created: 2008-01-10 Last updated: 2015-03-23Bibliographically approved

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