Protease-induced release of functional peptides from bioplexes
| Autor: | C. I. Edvard Smith, Gaza Salih, E Oscar Simonson, Lars Branden, Mathias G. Svahn |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Peptide Nucleic Acids
Cathepsin chemistry.chemical_classification Protease Peptide nucleic acid Polymers medicine.medical_treatment Serine Endopeptidases Pharmaceutical Science Peptide Transfection Biology Cathepsin L Kinetics Mice chemistry.chemical_compound Biochemistry chemistry Delayed-Action Preparations NIH 3T3 Cells medicine Nucleic acid biology.protein Animals Linker |
| Zdroj: | Journal of Controlled Release. 98:169-177 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2004.04.012 |
| Popis: | Linking peptide functions directly to nucleic acids can be used to improve transfection. We have previously demonstrated this by sequence-specific hybridization of a bifunctional peptide nucleic acid (PNA) consisting of a nucleic acid binding moiety conjugated to a peptide. The resulting biological complex of PNA/DNA is called a Bioplex. The bifunctional PNA is continuously synthesized with one or more functional entities. For certain applications, it might be preferable to eliminate a functional entity after it has served its purpose. We have addressed this issue by adding a specific protease cleavage site to the construct. In this first approach, cathepsin L was used to cleave a linker sequence including a cathepsin L site: afrsaaq, thereby releasing the tri-peptide Arg-Gly-Asp (RGD) from the PNA anchor. In vitro and in vivo experiments showed an efficient cleavage of the peptide. Moreover, bifunctional PNA constructs were shown to retain activity of the second entity following removal of the first function. Since cathepsin L is ubiquitously expressed in eukaryotic cells and becomes active as the endosomal pH drops, inclusion of cathepsin sites makes it possible to remove functional entities in late endosomes/early lysosomes. |
| Databáze: | OpenAIRE |
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