Protease-induced release of functional peptides from bioplexes Journal Article


Authors: Svahn, M. G.; Salih, G.; Simonson, E. O.; Smith, C. I. E.; Branden, L. J.
Article Title: Protease-induced release of functional peptides from bioplexes
Abstract: 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. © 2004 Elsevier B.V. All rights reserved.
Keywords: controlled study; nonhuman; animal cell; mouse; animals; mice; ph; peptide; transfection; dna; regulatory mechanism; kinetics; serine endopeptidases; nucleic acids; proteinase; eukaryotic cell; nih 3t3 cells; arginylglycylaspartic acid; synthesis (chemical); complexation; drug release; endosome; cells; experiments; polymers; cathepsin l; delayed-action preparations; inclusions; priority journal; article; endosomal release; enzymatic release; peptide nucleic acid; bioplexes; cathepsin sites; functional entity; peptide nucleic acids
Journal Title: Journal of Controlled Release
Volume: 98
Issue: 1
ISSN: 0168-3659
Publisher: Elsevier B.V.  
Date Published: 2004-07-23
Start Page: 169
End Page: 177
Language: English
DOI: 10.1016/j.jconrel.2004.04.012
PROVIDER: scopus
PUBMED: 15245898
DOI/URL:
Notes: J. Control. Release -- Cited By (since 1996):7 -- Export Date: 16 June 2014 -- CODEN: JCREE -- Source: Scopus
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